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1.
Respirology ; 29(3): 228-234, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37779266

RESUMO

BACKGROUND AND OBJECTIVE: The acute-phase protein C-reactive protein (CRP) is known to be associated with poor outcomes in cancer and cardiovascular disease, but there is limited evidence of its prognostic implications in interstitial lung diseases (ILDs). We therefore set out to test whether baseline serum CRP levels are associated with mortality in four different ILDs. METHODS: In this retrospective study, clinically measured CRP levels, as well as baseline demographics and lung function measures, were collected for ILD patients first presenting to the Royal Brompton Hospital between January 2010 and December 2019. Cox regression analysis was used to determine the relationship with 5-year mortality. RESULTS: Patients included in the study were: idiopathic pulmonary fibrosis (IPF) n = 422, fibrotic hypersensitivity pneumonitis (fHP) n = 233, rheumatoid arthritis associated ILD (RA-ILD) n = 111 and Systemic Sclerosis associated ILD (SSc-ILD) n = 86. Patients with a recent history of infection were excluded. Higher CRP levels were associated with shorter 5-year survival in all four disease groups on both univariable analyses, and after adjusting for age, gender, smoking history, immunosuppressive therapy and baseline disease severity (IPF: HR (95% CI): 1.3 (1.1-1.5), p = 0.003, fHP: 1.5 (1.2-1.9), p = 0.001, RA-ILD: 1.4 (1.1-1.84), p = 0.01 and SSc-ILD: 2.7 (1.6-4.5), p < 0.001). CONCLUSION: Higher CRP levels are independently associated with reduced 5-year survival in IPF, fHP, RA-ILD and SSc-ILD.


Assuntos
Artrite Reumatoide , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Proteína C-Reativa , Estudos Retrospectivos , Prognóstico , Artrite Reumatoide/complicações
2.
Biomedicines ; 11(7)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37509473

RESUMO

INTRODUCTION: Patients with pulmonary fibrosis experience early oxyhemoglobin desaturation under effort, which limits their ability to exercise and their quality of life. Recent studies have shown that in resting normoxaemic patients who become hypoxemic under exertion, administration of outpatient oxygen significantly improves stress dyspnoea and quality of life. It is unclear how this happens, since oxygen administration does not act directly on dyspnoea, and does not appear to have much effect on the heart rate and pulmonary artery pressure. We tested the hypothesis that correcting the hypoxaemia could reduce the increase in respiratory effort during the 6 min walking test, recording the breathing pattern during administration of oxygen or placebo. METHODS: We evaluated 20 patients with fibrotic interstitial lung diseases (17 males and 3 females; mean age 72 ± 2 years; M ± SE) with a resting SpO2 ≥92 that fell to ≤88% during the 6 min walk test (6MWT). After first establishing the oxygen flow necessary to prevent desaturation, the patients underwent two further 6MWT, 15-20 min apart, one with administration of medical air and one with oxygen at the same flow, in randomized double-blind order. During the test, SpO2, heart rate, respiratory rate, tidal volume and minute ventilation (VE) were recorded, using a Spiropalm spirometer (Cosmed, Rome, Italy). RESULTS: Oxygen saturation during the 6MWT decreased to a minimum value of 82.3% (95% CI 80.1-84.5%) during placebo and to 92% (90.3-93.7%) during oxygen with an average difference of 9.7% (7.8-11.6%, p < 0.0001). On the contrary, heart rate showed an increasing trend with walking time reaching a significantly higher maximum rate during placebo, with a difference of 5.4 bpm (2.9-8.7, p < 0.005) compared to oxygen. The distance walked was slightly but significantly greater after oxygen by 28 m (2-53, p < 0.05) and end of test dyspnoea after placebo by 0.6 points (0.1-1.1, p < 0.05). Respiratory rate increased over time, without differences between oxygen and placebo in the first minute of walking, then increasing significantly more during placebo (p < 0.0005). With placebo, tidal volume increased rapidly reaching a plateau at about 48% of FVC after 3 min, while with oxygen, the increase was slower, reaching a maximum of about 45% of FVC at the end of the test. Nevertheless, the difference was highly significant (p < 0.0005) at all the time points. Minute ventilation also increased significantly with walking time but remained at a highly significant lower level during oxygen than placebo at all the time points. Mean reduction in VE during the test with oxygen compared to placebo was 4.4 L/min (3.9-4.9, p < 0.0005). CONCLUSION: In our ILD patients, administration of outpatient oxygen during walking was related to a reduced increase in heart rate, respiratory rate, tidal volume and minute ventilation necessary to meet increased oxygen requirements, resulting in a lower workload on the cardiovascular system and on respiratory muscles and a consequent reduction in dyspnoea.

3.
Pulm Ther ; 9(2): 223-236, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36790678

RESUMO

INTRODUCTION: Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. METHODS: After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course. RESULTS: Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course. CONCLUSION: We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.

5.
Biomedicines ; 10(8)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36009520

RESUMO

Background: Nintedanib is an oral multitarget tyrosine kinase inhibitor approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Recent evidence demonstrated that nintedanib reduced functional disease progression also in subjects with non-IPF progressive fibrosing interstitial lung disease (PF-ILD). However, real-life data on the effectiveness of nintedanib in PF-ILD and familial pulmonary fibrosis (FPF) are lacking. Methods: this retrospective monocentric study enrolled 197 patients affected with IPF, PF-ILD and FPF treated with nintedanib at the Referral Centre of Siena from 2014 to 2021. Pulmonary functional tests and survival data were collected throughout the observation period for the evaluation of mortality and disease progression outcomes. Results: nintedanib treatment significantly reduced the FVC decline rate in IPF and PF-ILD subgroups, but not in FPF subjects. No significant differences were observed among the subgroups in terms of survival, which appeared to be influenced by gender and impaired lung function (FVC < 70% of predicted value). Concerning disease progression rate, a diagnosis of FPF is associated with more pronounced FVC decline despite nintedanib treatment. Conclusions: our research studies the effectiveness and safety of nintedanib in reducing functional disease progression of IPF and PF-ILD. FPF appeared to be less responsive to nintedanib, even though no differences were observed in terms of survival.

6.
Lung ; 200(4): 513-522, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35794392

RESUMO

BACKGROUND: Cytomegalovirus (CMV) is the major and most common opportunistic infection complicating lung transplant (LTX). The aim of this study was to analyse the epidemiological aspects of CMV infection in lung transplant patients subject to a pre-emptive anti-CMV approach and to study the impact of this infection on lung transplant outcome, in terms of onset of chronic lung allograft dysfunction (CLAD). METHODS: This single-centre retrospective study enrolled 87 LTX patients (median age 55.81 years; 41 females, 23 single LTX, 64 bilateral LTX). All patients were managed with a pre-emptive anti-CMV approach. The incidences of the first episode of CMV infection, 1, 3, 6 and 12 months after LTX, were 12.64%, 44.26%, 50.77% and 56.14%. A median interval of 41 days elapsed between LTX and the first episode of CMV infection. The median blood load of CMV-DNA at diagnosis was 20,385 cp/ml; in 67.64% of cases, it was also the peak value. Patients who had at least one episode had shorter CLAD-free survival. Patients who had three or more episodes of CMV infection had the worst outcome. RESULTS: CMV infection was confirmed to be a common event in lung transplant patients, particularly in the first three months after transplant. It had a negative impact on transplant outcome, being a major risk factor for CLAD. The hypothesis that lower viral replication thresholds may increase the risk of CLAD is interesting and deserves further investigation.


Assuntos
Infecções por Citomegalovirus , Transplante de Pulmão , Aloenxertos , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Life (Basel) ; 12(7)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35888169

RESUMO

INTRODUCTION: Cytomegalovirus (CMV) is the leading opportunistic infection in lung transplant (LTx) recipients. CMV is associated with graft failure and decreased survival. Recently, new antiviral therapies have been proposed. The present study aimed to investigate NK and T cell subsets of patients awaiting LTx. We analyzed the cellular populations between reactive and non-reactive QuantiFERON (QF) CMV patients for the prediction of immunological response to infection. METHODS: Seventeen pre-LTx patients and 15 healthy controls (HC) have been enrolled. QF and IFN-γ ELISA assay detections were applied. NK cell subsets and T cell and proliferation assay were detected before and after stimulation with pp-65 and IE-1 CMV antigens after stratification as QF+ and QF-. Furthermore, we quantified the serum concentrations of NK- and T-related cytokines by bead-based multiplex analysis. RESULTS: CD56brCD16lowNKG2A+KIR+ resulted in the best discriminatory cellular subsets between pre-LTx and HC. Discrepancies emerged between serology and QF assay. Better proliferative capability emerged from patients who were QF+, in particular in CD8 and CD25-activated cells. CD56brCD16low, adaptive/memory-like NK and CD8Teff were highly increased only in QF+ patients. CONCLUSIONS: QF more than serology is useful in the detection of patients able to respond to viral infection. This study provides new insights in terms of immunological responses to CMV in pre-LTX patients, particularly in NK and T cells biology.

8.
Biomolecules ; 12(5)2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35625645

RESUMO

Introduction: ILDs are a varied group of diffuse parenchymal lung diseases associated with high morbidity and mortality. Current treatments can only slow their progression but not cure the disease. Other treatments such as oxygen therapy can also be used as support. We know very little about the effects of oxygen therapy on patients with ILDs. The aim of this study was to collect data from the literature in order to determine whether oxygen therapy can actually decrease the mortality rate or whether it is only suitable for supportive therapy for patients with ILDs. Methods: We reviewed the literature since 2010 on oxygen therapy during exercise in patients with ILDs. Studies that used cardio-pulmonary tests were excluded. We only reviewed those that used the 6 min walking test (6MWT) or the free walking test. We located 11 relevant articles. Results: All the articles except a Japanese study showed an augmentation in oxyhaemoglobin saturation during exercise when oxygen was supplied. A 2018 study called AmbOx provided important data on the effects of oxygen therapy during daily activities, showing significant improvements in quality of life. Conclusions: This review showed that the literature on the benefits of oxygen therapy in patients with ILDs does not provide sufficient evidence to draft specific guidelines. It was not possible to conclude whether oxygen therapy has an effect on mortality or can only play a supportive role.


Assuntos
Doenças Pulmonares Intersticiais , Qualidade de Vida , Exercício Físico , Humanos , Doenças Pulmonares Intersticiais/terapia , Terapias Mente-Corpo , Oxigênio/uso terapêutico
9.
Front Pharmacol ; 13: 748931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308222

RESUMO

The pathogenetic mechanism of post-Covid-19 pulmonary fibrosis is currently a topic of intense research interest, but still largely unexplored. The aim of this work was to carry out a systematic exploratory search of the literature (Scoping review) to identify and systematize the main pathogenetic mechanisms that are believed to be involved in this phenomenon, in order to highlight the same molecular aspect of the lung. These aims could be essential in the future for therapeutic management. We identified all primary studies involving in post COVID19 syndrome with pulmonary fibrosis as a primary endpoint by performing data searches in various systematic review databases. Two reviewers independently reviewed all abstracts (398) and full text data. The quality of study has been assess through SANRA protocol. A total of 32 studies involving were included, included the possible involvement of inflammatory cytokines, concerned the renin-angiotensin system, the potential role of galectin-3, epithelial injuries in fibrosis, alveolar type 2 involvement, Neutrophil extracellular traps (NETs) and the others implied other specific aspects (relationship with clinical and mechanical factors, epithelial transition mesenchymal, TGF-ß signaling pathway, midkine, caspase and macrophages, genetics). In most cases, these were narrative reviews or letters to the editor, except for 10 articles, which presented original data, albeit sometimes in experimental models. From the development of these researches, progress in the knowledge of the phenomenon and hopefully in its prevention and therapy may originate.

10.
Minerva Med ; 113(3): 526-531, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32407050

RESUMO

BACKGROUND: THIS is the first time that a bronchoalveolar lavage (BAL) neutrophil-to-lymphocyte ratio (NL-ratio) has been demonstrated in sarcoidosis and chronic hypersensitivity pneumonitis (cHP) than in idiopathic pulmonary fibrosis (IPF) patients. METHODS: Consecutive BAL samples from the 167 interstitial lung disease (ILD) patients were retrospectively enrolled in the study and clustered into three diagnostic categories: IPF, cHP and sarcoidosis. RESULTS: NL-ratio which proved higher in IPF (mean±SD, 2.1±3.8) than sarcoidosis (mean±SD 0.7±1.9; P<1E-04) and cHP patients (mean±SD 1.6±3.1; P=7.7E-03). ROC curve analysis to discriminate between Sarcoidosis and other ILDs showed an area under the curve (AUC) of 83.7%, (56% sensitivity and 96% specificity) while IPF and the other ILD were discriminated with AUC of 73% using a NL-ratio threshold value of 0.48 (73% sensitivity and 63% specificity). Interestingly, the NL-ratio was significantly correlated with other prognostic parameters: it was inversely correlated with forced vital capacity (FVC) (r=-0.3; P=2.5E-02) and forced expiration volume in 1 second (FEV1) (r=-0.3; P=2E-02) percentages and directly correlated with composite pulmonary index (CPI) score (r=0.3; P=3.2E-02). A decision-tree statistical algorithm was applied. CONCLUSIONS: This is the first time that a lower NL-ratio has been demonstrated in sarcoidosis and cHP than in IPF patients. The present preliminary report indicates a relationship between BAL NL-ratio and lung function parameters in patients with IPF: this ratio may help to optimize management of IPF patients and to improve follow-up and outcome.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Sarcoidose , Biomarcadores , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Linfócitos , Neutrófilos , Prognóstico , Estudos Retrospectivos
11.
Panminerva Med ; 64(4): 548-554, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33274906

RESUMO

Fibrotic hypersensitivity pneumonitis (fHP) is a frequently misdiagnosed fibrosing interstitial pneumonia, which often remains undiagnosed due to the lack of uniformity of diagnostic criteria. Its features are similar to those of other ILDs, especially idiopathic pulmonary fibrosis (IPF), and biomarkers with potential clinical value have been proposed. We reviewed the recent literature on serum and BAL biomarkers, focusing on their clinical role in the diagnosis and management of fHP. We searched Medline/Pubmed results from 2005 until April 2020. The manuscripts of interest selected by our search were limited in number and proposed different clinical biomarkers in serum (IgG antibodies, macrophage inflammatory proteins-1, epithelial cell proteins) and BAL (lymphocytes, T-cell mediators). This is the first review to summarize all the serum and BAL biomarkers for fHP proposed in the literature. This review summarized the main biomarkers investigated in fibrotic hypersensitivity pneumonitis because an urgent aim of subsequent research will be to validate and standardize them for diagnostic purposes.


Assuntos
Alveolite Alérgica Extrínseca , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Biomarcadores , Fibrose , Alveolite Alérgica Extrínseca/diagnóstico
13.
Cells ; 10(11)2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34831404

RESUMO

Severe acute respiratory syndrome caused by coronavirus 2 emerged in Wuhan (China) in December 2019 and has severely challenged the human population. NK and T cells are involved in the progression of COVID-19 infection through the ability of NK cells to modulate T-cell responses, and by the stimulation of cytokine release. No detailed investigation of the NK cell landscape in clinical SARS-CoV-2 infection has yet been reported. A total of 35 COVID-19 hospitalised patients were stratified for clinical severity and 17 healthy subjects were enrolled. NK cell subsets and T cell subsets were analysed with flow cytometry. Serum cytokines were detected with a bead-based multiplex assay. Fewer CD56dimCD16brightNKG2A+NK cells and a parallel increase in the CD56+CD69+NK, CD56+PD-1+NK, CD56+NKp44+NK subset were reported in COVID-19 than HC. A significantly higher adaptive/memory-like NK cell frequency in patients with severe disease than in those with mild and moderate phenotypes were reported. Moreover, adaptive/memory-like NK cell frequencies were significantly higher in patients who died than in survivors. Severe COVID-19 patients showed higher serum concentrations of IL-6 than mild and control groups. Direct correlation emerged for IL-6 and adaptive/memory-like NK. All these findings provide new insights into the immune response of patients with COVID-19. In particular, they demonstrate activation of NK through overexpression of CD69 and CD25 and show that PD-1 inhibitory signalling maintains an exhausted phenotype in NK cells. These results suggest that adaptive/memory-like NK cells could be the basis of promising targeted therapy for future viral infections.


Assuntos
COVID-19/imunologia , Células Matadoras Naturais/citologia , Linfócitos T/citologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Citocinas/sangue , Feminino , Hospitalização , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Índice de Gravidade de Doença
14.
Antioxidants (Basel) ; 10(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34572982

RESUMO

Since SARS-CoV-2 emerged in 2019, strict monitoring of post-COVID-19 patients in order to ensure the early detection of sequelae and/or chronic organ damage that could been associated with the infection has been essential. Potential involvement of the NO pathway in the development of post-COVID-19 lung fibrotic alterations is feasible, since the majority of respiratory cells can produce NO, and fractional exhaled NO (FeNO) represents a biomarker of airway inflammation. The aim of this study was to investigate the potential utility of multiple-flow FeNO parameters in a post-COVID-19 population and to compare it with other indicators of lung damage proposed in the literature. We enrolled 20 patients hospitalized for COVID-19, who underwent clinical, respiratory functional (including PFTs and FeNO) and radiological follow-up after discharge. Compared with age- and sex-matched healthy controls, post-COVID-19 patients showed significantly higher FeNO 350 mL/s and CaNO levels. Moreover, among the parameters included in the follow-up, CaNO showed the best accuracy in indicating predominant fibrotic changes and GGO at CT scan. To our knowledge, this preliminary study has investigated for the first time multiple-flow FeNO parameters in a post-COVID-19 population. The evidence of increased CaNO values may imply the persistence of alveolar and bronchiolar inflammation and/or a mild impairment of the alveolar-capillary membrane in these patients.

15.
Clin Immunol ; 230: 108827, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34428741

RESUMO

BAL cellularity and lymphocyte immunophenotyping offer insights into lung inflammatory status. Natural killer (NK) cells are efficient effector cells, producing pro-inflammatory cytokines. A better understanding of the biology of NK cells in BAL in the lungs is necessary to improve the pathogenesis of fibrotic ILD and develop prospective targeted treatments. Our aim was to analyse NK and NKT-like cell percentages in BAL from 159 patients with different ILD: f-HP, f-NSIP, IPF and CTD-ILD, to evaluate their potential diagnostic/prognostic role. BAL NK cell percentages showed significantly higher values in IPF than in f-HP and f-NSIP, while BAL NKT-like cells showed significantly lower values in the f-NSIP than the f-HP and IPF. A cut-off of 4%NK cells in BAL of IPF showed a significant difference in survival rate. It suggests a possible new marker of survival and raises the possibility of new targeted approach in treatment and management of IPF.


Assuntos
Células Matadoras Naturais/imunologia , Doenças Pulmonares Intersticiais/imunologia , Idoso , Idoso de 80 Anos ou mais , Alveolite Alérgica Extrínseca/imunologia , Alveolite Alérgica Extrínseca/patologia , Alveolite Alérgica Extrínseca/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/fisiopatologia , Feminino , Fibrose , Humanos , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/fisiopatologia , Imunofenotipagem , Estimativa de Kaplan-Meier , Células Matadoras Naturais/classificação , Células Matadoras Naturais/patologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/classificação , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/patologia , Prognóstico , Testes de Função Respiratória
16.
Mol Diagn Ther ; 25(5): 593-605, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34342843

RESUMO

BACKGROUND: Severe allergic asthma (SAA) is based on type 2 (T2-high) immune responses to allergens promoting type 2 T helper (Th2) cell cytokine responses and production of IgE antibodies. Omalizumab was the first biological drug licensed for clinical use in the management of IgE-mediated SAA. Despite emerging evidence supporting the prominent role of follicular T cells (Tfh), Breg and Treg subsets, in the development and progression of SAA, no data are available on the impact of omalizumab therapy. METHODS: Ten SAA patients monitored at the Respiratory Diseases Unit of Siena University Hospital and ten healthy sex- and age-matched controls were enrolled in the study. Clinical and functional parameters were collected at baseline (T0) and after 6 months of therapy (T6). Cellular population analysis was determined through multicolour flow cytometry. RESULTS: SAA patients showed higher percentages of Th17.1, Tfh and Tfh2 while CD24hiCD27hi Breg cell, Treg and Tfr percentages were significantly lower than in controls. Higher percentages of Tfh2 in patients with nasal polyps than in those without and in controls were observed. At T6, significant decreases in Tfh and Tfh2 compared with T0 were observed. A slightly significant increase in Teffs was reported at T6 compared to T0. ΔIgE levels in serum were correlated with ΔCD19+CD24+CD27+ Breg cell percentages (r = - 0.86, p = 0.0022). CONCLUSIONS: Our data explored the changes in Tfh cells, Tregs and Bregs in severe asthma. The restoration of immunological imbalance in SAA patients after omalizumab is certainly intriguing and represents a glimpse into the comprehension of immunological effects of treatment.


Assuntos
Asma , Linfócitos B Reguladores , Asma/tratamento farmacológico , Humanos , Omalizumab/uso terapêutico , Linfócitos T Reguladores , Células Th2
17.
Sarcoidosis Vasc Diffuse Lung Dis ; 38(2): e2021007, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34316252

RESUMO

Sarcoidosis is a heterogeneous granulomatous disease. Biological markers and clinical features could allow specific phenotypes to be associated with different prognosis, severity and treatment responses. This retrospective multicentre study aims to analyse the clinical and immunological features of sarcoidosis and to identify a routine non-invasive biomarker useful in clinical practice. MATERIALS AND METHODS: 129 Caucasian patients with sarcoidosis (median age IQR, 56 (47-62)) were enrolled retrospectively in the study. Medical history, routine laboratory findings, lung function results and radiological features from the last examination of October 2019 - February 2020 were gathered from the patients' clinical records. RESULTS: Regardless their clinical status at disease onset, at the last clinical examination we didn't observe any differences in terms of therapeutic management between symptomatic and asymptomatic patients. Stratifying sarcoidosis population according to therapeutic management, the N/L ratio was higher in the treated group than in the non-treated group (p=0.0034). Receiver operating curve (ROC) analysis distinguished these two groups according to N/L ratio with an area under the curve (AUC) of 65.3% and a best cut-off value of 2.21. Peripheral N/L ratio was significantly higher in radiological stages 2-4 than in stages 0-1 (p=0.0090) distinguishing these two groups with an AUC of 64% and a best cut-off value of 2.13. DISCUSSION: In our multicentric cohort study similar periodic follow-up can be suggested for symptomatic and asymptomatic sarcoidosis patients at onset. In the heterogeneous context of this disease, N/L ratio proved to be a useful and simple routine laboratory biomarker related to disease activity and need for treatment.

18.
Clin Exp Immunol ; 205(3): 406-416, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107064

RESUMO

Sarcoidosis is a multi-systemic granulomatous disease of unknown origin. Recent research has focused upon the role of autoimmunity in its development and progression. This study aimed to determine and define the disturbance and distribution of T and B cell subsets in the alveolar and peripheral compartments. Thirteen patients were selected for the study [median age, interquartile range (IQR) = 57 years (48-59); 23% were male]. Twelve healthy controls [median age, IQR = 53 years (52-65); 16% male] were also enrolled into the study. Cellular and cytokine patterns were measured using the cytofluorimetric approach. Peripheral CD8 percentages were higher in sarcoidosis patients (SP) than healthy controls (HC) (p = 0.0293), while CD4 percentages were lower (p = 0.0305). SP showed low bronchoalveolar lavage (BAL) percentages of CD19 (p = 0.0004) and CD8 (p = 0.0035), while CD19+ CD5+ CD27- percentages were higher (p = 0.0213); the same was found for CD4 (p = 0.0396), follicular regulatory T cells (Treg ) (p = 0.0078) and Treg (p < 0.0001) cells. Low T helper type 17 (Th17) percentages were observed in BAL (p = 0.0063) of SP. Peripheral CD4+ C-X-C chemokine receptor (CXCR)5+ CD45RA- ) percentages and follicular T helper cells (Tfh)-like Th1 (Tfh1) percentages (p = 0.0493 and p = 0.0305, respectively) were higher in the SP than HC. Tfh1 percentages and Tfh-like Th2 percentages were lower in BAL than in peripheral blood (p = 0.0370 and p = 0.0078, respectively), while CD4+ C-X-C motif CXCR5+ CD45RA- percentages were higher (p = 0.0011). This is the first study, to our knowledge, to demonstrate a link between an imbalance in circulating and alveolar Tfh cells, especially CCR4-, CXCR3- and CXCR5-expressing Tfh subsets in the development of sarcoidosis. These findings raise questions about the pathogenesis of sarcoidosis and may provide new directions for future clinical studies and treatment strategies.


Assuntos
Imunidade Adaptativa/imunologia , Subpopulações de Linfócitos B/imunologia , Sarcoidose Pulmonar/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Idoso , Autoimunidade/imunologia , Líquido da Lavagem Broncoalveolar/química , Antígenos CD8/análise , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur J Intern Med ; 89: 76-80, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33931268

RESUMO

BACKGROUND: Broncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases. OBJECTIVES: In our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed. METHODS: A retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital. The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature. RESULTS: Among ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT. CONCLUSION: The analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Estudos Retrospectivos
20.
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
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