Prognostic Biomarkers of Sarcoidosis: A Comparative Study of Serum Chitotriosidase, ACE, Lysozyme, and KL-6

Purpose. Sarcoidosis is a systemic granulomatous disease with unknown etiology. Many clinical presentations have been reported, and acute disease needs to be distinguished from subacute and chronic disease. The unpredictable clinical course of the disease prompted us to evaluate the clinical utility of biomarker serum detection in sarcoidosis follow-up. Methods. Serum concentrations of chitotriosidase, ACE, KL-6, and lysozyme were analyzed by different methods in a population of 74 sarcoidosis patients (46 on steroid therapy at sampling) regularly monitored at Siena Sarcoidosis Regional Referral Centre and in a group of controls with the aim of comparing their contribution to clinical management of sarcoidosis patients. Results. KL-6 concentrations were significantly elevated in sarcoidosis patients with lung fibrosis and were significantly correlated with DLco and CPI score, while chitotriosidase was significantly higher in patients with extrapulmonary localizations. With a cut-off value of 303.5 IU/ml, KL-6 showed the best sensitivity (78%), while chitotriosidase reported the best specificity (85%) among the biomarkers. Conclusions. KL-6 is a reliable biomarker of fibrotic lung involvement in sarcoidosis patients. Among biomarkers, KL-6 showed the best sensitivity and serum chitotriosidase the best specificity, even in patients on chronic steroid therapy, and seemed to correlate with extrapulmonary localizations

Valutazione funzionale,clinica e radiologica di pazienti affetti da polmonite interstiziale UIP e NSIP:la nostra casistica.

Questa tesi ha come scopo l'analisi retrospettiva delle caratteristiche demografiche, cliniche, funzionali, biologiche e di imaging di 84 pazienti affetti da polmoniti interstiziali idiopatiche e non a istotipo UIP e NSIP seguiti dal 1996 al 2011 presso l’ambulatorio dedicato alle interstiziopatie polmonari della Pneumologia Universitaria; la valutazione nello stesso gruppo di pazienti delle modificazioni funzionali e di imaging durante il periodo di follow-up; la Determinazione della validità delle caratteristiche basali e delle modificazioni funzionali e di imaging come valore prognostico nell’evoluzione della patologia,la valutazione della mortalità a 18 e 60 mesi.L'analisi è stata effettuata sui valori basali di fvc,svc,tlc,dlco ,Po2,Pco2 per quanto riguarda le caratteristiche funzionali,inoltre è stato valutato lo score tac per quanto riguarda le caratteristiche radiologiche.Le caratteristiche basali dei pazienti che abbiamo studiato sono sostanzialmente sovrapponibili a quelle descritte in letteratura, anche se con alcune differenze. L‟età media alla diagnosi nel totale dei pazienti risulta di 68+/- 8, e questo valore si mantiene anche suddividendolo nei due gruppi UIP e NSIP. Tale valore risulta più alto del valore trovato in altri studi, per esempio i pazienti analizzati da Travis e coll hanno un età media di 52 anni . La prevalenza del sesso femminile nella NSIP, l‟esposizione tabagica e le caratteristiche funzionali basali invece sono sovrapponibili alla letteratura. Abbiamo infatti una prevalenza del sesso femminile nella NSIP e una prevalenza del sesso maschile nella UIP. Anche nel nostro gruppo di pazienti l‟esposizione tabagica è prevalente, infatti il 52% dei pazienti è fumatore o ex fumatore e questa prevalenza si mantiene anche nei due gruppi.Analizzando le caratteristiche basali della funzione polmonare si osserva che i nostri valori basali di FVC e PO2 sono sovrapponibili ad altri lavori, mentre la DLCO dei nostri pazienti è più bassa.La valutazione dell‟andamento della funzione respiratoria durante il periodo di follow-up evidenzia come nel totale dei pazienti si ha un decremento di tutti i parametri funzionali.Valutando la lettura TC attraverso lo score radiologico, i punteggi radiologici espressi come anomalie complessive e suddivisi in tre gruppi ha evidenziato un aumento del rischio di mortalità cinque volte superiore nei pazienti con punteggio maggiore di 55 rispetto ai pazienti che presentano anomalie complessive minori di 35.Anche le analisi delle variazioni radiologiche nel follow up del nostro campione sono in accordo con la letteratura infatti i pazienti con quadro radiologico di UIP hanno ad un anno un aumento del TC score, delle anomalie complessive e dell‟ honey combing.I pazienti invece con caratteristiche radiologiche di NSIP al contrario hanno una riduzione dello score fibrotico e delle anomalie complessive.La nostra casistica ha riportato una percentuale di sopravvivenza a 18 mesi del 92% della NSIP e del 74 % nella UIP. La percentuale di sopravvivenza per i pazienti NSIP si mantiene costante nel tempo invece nel gruppo UIP si riduce progressivamente fino ad arrivare al 46% a 60 mesi. L‟esame della nostra casistica conferma l‟importanza sia della valutazione funzionale basale che del follow-up a breve termine degli indici funzionali. Il nostro studio evidenzia inoltre che a prescindere dalla classificazione UIP/NSIP lo score radiologico è importante come elemento prognostico della mortalità.Questo studio può fornire lo spunto per applicare routinariamente la metodica di score radiologico alla lettura delle immagini TC in pazienti con interstiziopatia polmonar

Serum amyloid A: A potential biomarker of lung disorders

Serum amyloid A is an acute-phase protein with multiple immunological functions. Serum amyloid A is involved in lipid metabolism, inflammatory reactions, granuloma formation, and cancerogenesis. Additionally, serum amyloid A is involved in the pathogenesis of different autoimmune lung diseases. The levels of serum amyloid A has been evaluated in biological fluids of patients with different lung diseases, including autoimmune disorders, chronic obstructive pulmonary diseases, obstructive sleep apnea syndrome, sarcoidosis, asthma, lung cancer, and other lung disorders, such as idiopathic pulmonary fibrosis, tuberculosis, radiation pneumonitis, and cystic fibrosis. This review focuses on the cellular and molecular interactions of serum amyloid A in different lung diseases and suggests this acute-phase protein as a prognostic marker

Rituximab Therapy in Interstitial Lung Disease associated with Rheumatoid Arthritis

Rheumatoid Arthrtitis (RA) is a chronic systemic inflammatory disease. In this disease interstitial lung involvement (ILD) is associated with high risk of mortality. Rituximab, a monoclonal antibody directed against CD20, is effective in the treatment of articular manifestations in RA while controversial results have been reported on Rituximab efficacy in RA-ILD patients. This study described the clinical and radiological characteristics of 28 patients with RA-ILD and analysed the efficacy of anti-CD20 therapy in 14 RA-ILD patients treated with this drug for more than 1 year. In our population, HRCT features revealed UIP in 15/28 (54%) of patients, NSIP in 8/28 (29%) patients, other patients presented fibroelastosis and nodular fibrotic patterns. Higher mortality rate was observed in RA patients with radiologic UIP pattern compared to those with different radiological patterns, although our patients with RA associated with radiological UIP pattern had a longer survival (7 years from ILD diagnosis) compared with literature data (3-5 years from ILD diagnosis). Half of our patients were treated with Rituximab and they had a progressive reduction of lung function parameters. After 6 and 12 months of anti-CD20 therapy our patients presented a stabilization of lung function parameters. In conclusion, our study supported the theory that patients with RA and radiological UIP pattern at CT scan presented the worst survival; Rituximab therapy seems to be effective stabilizing ILD involvement and lung function deterioration. This article is protected by copyright. All rights reserved

Pirfenidone therapy for familial pulmonary fibrosis: a real-life study.

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. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Idiopathic pulmonary fibrosis a rare disease with severe bone fragility

Idiopathic pulmonary fibrosis (IPF) is a rare form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The aim of this cross-sectional study was to assess the prevalence of osteoporosis and fragility fracture in a population of adults with IPF and to identify whether any possible clinical and pulmonary function parameters may be associated with increased bone fragility. In 58 IPF patients (mean age 65.1 ± 9.1 years), we measured bone mineral density (BMD) of the lumbar spine, the femoral neck, and the entire hip. Moreover, the presence of vertebral fractures on a lateral chest X-ray study was evaluated, and a vertebral fracture burden was quantified using the spinal deformity index (SDI). As expected, osteoporosis was significantly more frequent in females with respect to males (57.9 vs 20.5 %, respectively), whereas the fractures prevailed in males with respect to females (38.5 vs 26.3 %, respectively). There were positive correlations between BMD at all skeletal sites and respiratory parameters; in particular for FVC % and DLCO % with BMD at femoral sub-regions. Moreover, we compared the average of DLCO (%) measure by values of SDI score that was higher in those patients with lower values of DLCO (%). The study shows a high prevalence of fragility with vertebral fractures in IPF patients, especially in males. Moreover, the vertebral fracture burden is associated with a worsening of FVC (%) and DLCO (%). Therefore, an evaluation of bone status is recommended, especially in those patients who are candidates for lung transplantation

Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis

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

A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis

BACKGROUND: Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease. OBJECTIVES: This national, multicenter, retrospective real-life study was intended to determine the impact of nintedanib on the treatment of patients with severe IPF. METHODS: All patients included had severe IPF and had to have at least 6 months of follow-up before and at least 6 months of follow-up after starting nintedanib. The aim of the study was to compare the decline in lung function before and after treatment. Patient survival after 6 months of therapy with nintedanib was assessed. RESULTS: Forty-one patients with a forced vital capacity (FVC) 6450% and/or a diffusing capacity of the lung for carbon monoxide (DLCO) 6435% predicted at the start of nintedanib treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both absolute and % predicted) was significantly reduced compared to the pretreatment period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50, and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54, and 29.23%, respectively, p = 0.04). No significant beneficial effect was observed in the other functional parameters analyzed. The 1-year survival in this population was 79%, calculated from month 6 of therapy with nintedanib. CONCLUSIONS: This nationwide multicenter experience in patients with severe IPF shows that nintedanib slows down the rate of decline of absolute and % predicted DLCO but does not have significant impact on FVC or other lung parameters