Publications by authors named "Francesco Salton"

24 Publications

  • Page 1 of 1

The Updated Role of Ultrasound in Assessing Dermatological Manifestations in Systemic Sclerosis.

Open Access Rheumatol 2021 28;13:79-91. Epub 2021 Apr 28.

Unit of Pulmonology, University Hospital of Trieste, Trieste, Italy.

Systemic sclerosis (SSc), an autoimmune connective tissue disease, characterized by skin fibrosis, increased dermal thickness and microvascular involvement. Fibroblasts and myofibroblasts deposit excessive amounts of collagenous and non-collagenous extracellular matrix components in the skin. This leads to microvascular abnormalities and Raynaud's phenomenon, with painful digital ulcers (DU) at the fingertips adding to patient discomfort. The skin involvement and severity in SSc was evaluated by the Modified Rodnan skin score (mRSS). Although high-frequency ultrasound (HUS) has been widely researched in the study of skin thickness and DU in SSc, its adoption into clinical practice is not yet common. However, novel insights into the still relatively unknown disease pathogenesis in SSc and its evaluation may be provided by HUS, including early (pre-clinical) skin involvement. It may also be useful in both the evaluation and follow-up of DU. Indeed, it is a non-invasive, safe, inexpensive and reproducible method able to assess not only SSc patients' cutaneous structural changes, but also their vascular system changes. Moreover, several recent studies have reported that elastosonography (ES) is of use when investigating skin involvement in systemic sclerosis. This review aims at providing information as to role HUS and ES play in research advancements and the clinical perspectives in the evaluation of skin thickness and DU in SSc patients.
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http://dx.doi.org/10.2147/OARRR.S282612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092351PMC
April 2021

Evaluation of Correlations between Genetic Variants and High-Resolution Computed Tomography Patterns in Idiopathic Pulmonary Fibrosis.

Diagnostics (Basel) 2021 Apr 23;11(5). Epub 2021 Apr 23.

Department of Pulmonology, University Hospital of Cattinara, 34127 Trieste, Italy.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD). This prospective observational study aimed at the evaluation of any correlation between genetic variants associated with IPF susceptibility and high-resolution computed tomography (HRCT) patterns. It also aimed at evidencing any differences in the HRTC pattern between the familial and sporadic form at diagnosis and after two years.

Methods: A total of 65 IPF patients (mean age at diagnosis 65 ± 10) were enrolled after having given written informed consent. HRCT and genetic evaluations were performed.

Results: A total of 19 familial (mean age 62 ± 15) and 46 sporadic (mean age 70 ± 9) IPF patients were enrolled. A statistically significant difference was evidenced in the HRTC pattern at diagnosis between the two groups. Sporadic IPF patients had a predominantly usual interstitial pneumonia (UIP) pattern compared with those patients with familial IPF (60.0% vs. 21.1%, respectively). Moreover, familial IPF patients had more alternative diagnoses than those with sporadic IPF (31.6% vs. 2.2%, respectively). Furthermore, there was a slight increase in the typical UIP pattern in the familial IPF group at two years from diagnosis.

Conclusions: Genetic factors play a pivotal role in the risk of developing IPF. However, further studies are required to clarify how these genetic factors may guide clinical treatment decisions.
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http://dx.doi.org/10.3390/diagnostics11050762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146750PMC
April 2021

The Relationship between Pulmonary Damage and Peripheral Vascular Manifestations in Systemic Sclerosis Patients.

Pharmaceuticals (Basel) 2021 Apr 23;14(5). Epub 2021 Apr 23.

Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Firenze, 50121 Florence, Italy.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by the presence of generalized vasculopathy and tissue fibrosis. Collagen vascular disorder in SSc is due to fibroblast and endothelial cell dysfunctions. This leads to collagen overproduction, vascular impairment and immune system abnormalities and, in the last stage, multi-organ damage. Thus, to avoid organ damage, which has a poor prognosis, all patients should be carefully evaluated and followed. This is particularly important in the initial disease phase, so as to facilitate early identification of any organ involvement and to allow for appropriate therapy. Pulmonary disease in SSc mainly involves interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). High-resolution computed tomography (HRCT) and pulmonary function tests (PFT) have been proposed to monitor parenchymal damage. Although transthoracic echocardiography is the most commonly used screening tool for PAH in SSc patients, definitive diagnosis necessitates confirmation by right heart catheterization (RHC). Moreover, some studies have demonstrated that nailfold videocapillaroscopy (NVC) provides an accurate evaluation of the microvascular damage in SSc and is able to predict internal organ involvement, such as lung impairment. This review provides an overview of the correlation between lung damage and microvascular involvement in SSc patients.
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http://dx.doi.org/10.3390/ph14050403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145021PMC
April 2021

The History and Mystery of Alveolar Epithelial Type II Cells: Focus on Their Physiologic and Pathologic Role in Lung.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Pulmonology Department, University Hospital of Cattinara, 34128 Trieste, Italy.

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.
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http://dx.doi.org/10.3390/ijms22052566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961977PMC
March 2021

The Treatment of Lung Involvement in Systemic Sclerosis.

Pharmaceuticals (Basel) 2021 Feb 13;14(2). Epub 2021 Feb 13.

Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Firenze, 50121 Firenze FI, Italy.

Systemic sclerosis (SSc) patients are often affected by interstitial lung disease (ILD) and, although there have been recent treatment advances, it remains the leading cause of death among SSc, with a 10-year mortality up to 40%. African Americans and subjects with diffuse cutaneous SSc or anti-topoisomerase 1 antibodies are most commonly affected. Currently, early ILD diagnosis can be made, and it is pivotal to improve the prognosis. The diagnostic mainstay test for SSc-ILD is high-resolution computed tomography for the morphology and pulmonary function tests for the functional aspects. Treatment planning and intensity are guided by the disease severity and risk of progression. Traditionally, therapy has depended on combinations of immunosuppressants, particularly cyclophosphamide and mycophenolate mofetil, which can be supplemented by targeted biological and antifibrotic therapies. Benefits have been observed in trials on hematopoietic autologous stem cell transplantation for patients with progressive SSc, whilst lung transplantation is reserved for refractory SSc-ILD cases. Herein, recent advances in SSc-ILD treatment will be explored.
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http://dx.doi.org/10.3390/ph14020154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918752PMC
February 2021

C1q-HA Matrix Regulates the Local Synthesis of Hyaluronan in Malignant Pleural Mesothelioma by Modulating HAS3 Expression.

Cancers (Basel) 2021 Jan 22;13(3). Epub 2021 Jan 22.

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.

Increased hyaluronic acid (HA) production is often associated with cancer progression. In malignant pleural mesothelioma (MPM), HA is found at elevated levels in pleural effusions and sera of patients, and it has been widely debated whether MPM cells are able to produce HA by themselves or through the release of growth factors stimulating other cells. Another key component of the MPM microenvironment is C1q, which can act as a pro-tumorigenic factor favoring cell adhesion, migration and proliferation. The aim of the current study was to prove that MPM primary cells are able to synthesize HA and to inquire the stimulus given by C1q-HA matrix to HA synthesis. We confirmed the presence of a HA coat and cable-like structures around MPM primary cells, as well as an intracellular pool, mainly localized in the cytoplasmic and perinuclear region. After evaluating HA synthase (HAS) enzymes' basal expression in MPM primary cells, we found that C1q bound to HA was able to impinge upon HA homeostasis by upregulating HAS3 both at the mRNA and the protein levels. High expression of has been correlated with a shorter life expectancy in MPM by bioinformatical analysis. These data confirmed that C1q bound to HA may exert pro-tumorigenic activity and identified HAS3 as a potential target in MPM.
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http://dx.doi.org/10.3390/cancers13030416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865933PMC
January 2021

What Role Does Trabecular Bone Score Play in Chronic Inflammatory Rheumatic Diseases?

Front Med (Lausanne) 2020 30;7:600697. Epub 2020 Nov 30.

Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy.

Patients suffering from rheumatic inflammatory diseases, e.g., systemic sclerosis, rheumatoid arthritis, and ankylosing spondylitis, are at risk of low bone mass. Dual-energy X-ray Absorptiometry (DXA) is the traditional radiological measurement technique for bone mineral density (BMD). The recently developed trabecular bone score (TBS) enhances the skeletal information provided by standard BMD. It re-analyzes the spatial dynamics of pixel intensity changes in lumbar spine DXA images, defining a quantitative index, characterizing trabecular bone microarchitecture. It has been demonstrated that low TBS values are associated with an increased incidence of fractures in patients with rheumatic diseases. These methods used together for bone damage evaluation can be of value to identify individuals who will potentially fracture. The main scientific literature on the clinical aspects of osteoporosis, including the use of TBS in evaluating this pathology, are herein reported aimed at shedding light on the role trabecular bone score plays in chronic inflammatory rheumatic diseases.
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http://dx.doi.org/10.3389/fmed.2020.600697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793927PMC
November 2020

Epithelial-Mesenchymal Transition: A Major Pathogenic Driver in Idiopathic Pulmonary Fibrosis?

Medicina (Kaunas) 2020 Nov 13;56(11). Epub 2020 Nov 13.

Pulmonology Department, University Hospital of Cattinara, 34149 Trieste, Italy.

Despite the fact that epithelial-mesenchymal transition (EMT) is a common downstream mechanism of all fibrosing diseases, whether it represents a leading process in the development of idiopathic pulmonary fibrosis has been widely discussed and is still a matter of debate. According to the most recent advances, EMT is thought to be mainly driven by the overexpression of several developmental pathways upstream of dysfunctional epithelial regeneration, which indeed normally occurs after damage and during tissue turnover. Future research should likely be directed at investigating the molecular mechanisms underlying epithelial dysfunction, in order to allow for both the removal of the wording "idiopathic" from idiopathic pulmonary fibrosis ("IPF") and for the identification of earlier and more effective therapeutic targets than the late process of fibrosis.
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http://dx.doi.org/10.3390/medicina56110608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697350PMC
November 2020

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

Open Forum Infect Dis 2020 Oct 12;7(10):ofaa421. Epub 2020 Sep 12.

Pulmonology Department, S. Maria della Misericordia University Hospital, Udine, Italy.

Background: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality.

Methods: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels.

Results: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 ( = .07) and 14 vs 26 ( = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8;  = .001). Study treatment was associated with rapid improvement in PaO:FiO and CRP levels. The complication rate was similar for the 2 groups ( = .84).

Conclusion: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. ClinicalTrials.gov NCT04323592.
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http://dx.doi.org/10.1093/ofid/ofaa421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543560PMC
October 2020

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis.

J Clin Med 2020 Sep 21;9(9). Epub 2020 Sep 21.

Department of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy.

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, "real life" study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.
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http://dx.doi.org/10.3390/jcm9093033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565737PMC
September 2020

Factors limiting the utility of bronchoalveolar lavage in the diagnosis of COVID-19.

Eur Respir J 2020 11 5;56(5). Epub 2020 Nov 5.

Pulmonology Unit, University Hospital of Trieste, Trieste, Italy.

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http://dx.doi.org/10.1183/13993003.03383-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507584PMC
November 2020

Interstitial lung disease in patients with antisynthetase syndrome: a retrospective case series study.

Jpn J Radiol 2021 Jan 2;39(1):40-46. Epub 2020 Sep 2.

Department of Radiology, University of Trieste, Strada di Fiume 447, 34128, Trieste, Italy.

Purpose: Antisynthetase syndrome (ASS) is a rare systemic autoimmune condition associated to the presence of anti-aminoacyl-tRNA synthetase antibodies. Interstitial lung disease (ILD) is the most prevalent manifestation of ASS and is a major determinant of morbidity and mortality. The aim of this study was to describe the radiological characteristics of patients with ASS-associated-ILD in our institution.

Materials And Methods: Medical records from 2014 to 2020 were retrospectively reviewed and patients with a diagnosis of ASS and evidence of ILD on HRCT were included. HRCT images were reviewed by two thoracic radiologists in consensus. Five HRCT patterns were defined: cellular non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), mixed NSIP/OP pattern, acute interstitial pneumonia (AIP) pattern and fibrotic pattern. Descriptive statistics was calculated for all variables.

Results: Twenty-two patients with ASS who met inclusion criteria were included. The disease presented with the typical triad of ASS in 45% of patients, 55% had ILD only at the onset. Cellular NSIP was present in 27% of patients, OP in 23%, mixed NSIP/OP in 9%, AIP in 18% and a fibrotic pattern in 23%.

Conclusion: HRCT findings in ASS-associated ILD are often non-specific; nevertheless, it is important to consider this diagnosis, especially in patients presenting with acute onset of symptoms.
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http://dx.doi.org/10.1007/s11604-020-01030-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813732PMC
January 2021

Monitoring the microcirculation in the diagnosis and follow-up of systemic sclerosis patients: Focus on pulmonary and peripheral vascular manifestations.

Microcirculation 2020 11 26;27(8):e12647. Epub 2020 Jul 26.

Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

Systemic sclerosis (SSc) is a connective tissue disease, characterized by vascular damage and progressive fibrosis, affecting the skin and internal organs. The vascular changes include functional and structural abnormalities in the microcirculation, which play a central role not only in diagnosis but also in the prognosis and follow-up of systemic sclerosis patients. Nailfold videocapillaroscopy (NVC) is a safe, validated, noninvasive, inexpensive, reliable, and reproducible method that allows for the evaluation of structural changes in scleroderma microangiopathy. However, capillary blood flow/perfusion cannot be measured by NVC under standard conditions and, consequently, must rely on various laser techniques and thermography for the assessment and quantification of cutaneous blood perfusion. Other emerging technologies, such as optical Doppler tomography and spectroscopy, may be used to evaluate the skin flow. This review updates current knowledge on the use of microvascular evaluation techniques in SSc, including complications such as digital ulcers and pulmonary arterial hypertension.
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http://dx.doi.org/10.1111/micc.12647DOI Listing
November 2020

Nintedanib Treatment for Idiopathic Pulmonary Fibrosis Patients Who Have Been Switched from Pirfenidone Therapy: A Retrospective Case Series Study.

J Clin Med 2020 Feb 4;9(2). Epub 2020 Feb 4.

Pneumology Unit, Dept. of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy.

Background: The efficacy and effectiveness of nintedanib as a first-line therapy in idiopathic pulmonary fibrosis (IPF) patients have been demonstrated by clinical trials and real-life studies. Our aim was to examine the safety profile and effectiveness of nintedanib when it is utilized as a second-line treatment in subjects who have discontinued pirfenidone.

Methods: The medical charts of 12 patients who were switched from pirfenidone to nintedanib were examined retrospectively. The drug's safety was defined by the number of adverse events (AEs) that were reported; disease progression was evaluated based on the patient's vital status and changes in forced vital capacity (FVC) at 12-month follow-up.

Results: The numbers of patients experiencing AEs and of the AEs per patient in our study group didn't significantly differ with respect to a group of 56 individuals who were taking nintedanib as a first-line therapy during the study period (5/12 vs. 22/56; = 0.9999, and 0.00 (0.00-1.00) vs. 0.00 (0.00-3.00); = 0.517, respectively). Two out of the 3 patients who had been switched to nintedanib due to a rapid disease progression showed stabilized FVC values.

Conclusions: Nintedanib was found to have an acceptable safety profile in the majority of the IPF patients switched from pirfenidone. Prospective studies are warranted to determine if the drug can effectively delay disease progression in these patients.
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http://dx.doi.org/10.3390/jcm9020422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074103PMC
February 2020

miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation.

ERJ Open Res 2019 Oct 16;5(4). Epub 2019 Dec 16.

Pulmonology Dept, University Hospital of Cattinara, Trieste, Italy.

Rationale: Alveolar type II (ATII) cells act as adult stem cells contributing to alveolar type I (ATI) cell renewal and play a major role in idiopathic pulmonary fibrosis (IPF), as supported by familial cases harbouring mutations in genes specifically expressed by these cells. During IPF, ATII cells lose their regenerative potential and aberrantly express pathways contributing to epithelial-mesenchymal transition (EMT). The microRNA miR-200 family is downregulated in IPF, but its effect on human IPF ATII cells remains unproven. We wanted to 1) evaluate the characteristics and transdifferentiating ability of IPF ATII cells, and 2) test whether miR-200 family members can rescue the regenerative potential of fibrotic ATII cells.

Methods: ATII cells were isolated from control or IPF lungs and cultured in conditions promoting their transdifferentiation into ATI cells. Cells were either phenotypically monitored over time or transfected with miR-200 family members to evaluate the microRNA effect on the expression of transdifferentiation, senescence and EMT markers.

Results: IPF ATII cells show a senescent phenotype (p16 and p21), overexpression of EMT (ZEB1/2) and impaired expression of ATI cell markers (AQP5 and HOPX) after 6 days of culture in differentiating medium. Transfection with certain miR-200 family members (particularly miR-200b-3p and miR-200c-3p) reduced senescence marker expression and restored the ability to transdifferentiate into ATI cells.

Conclusions: We demonstrated that ATII cells from IPF patients express senescence and EMT markers, and display a reduced ability to transdifferentiate into ATI cells. Transfection with certain miR-200 family members rescues this phenotype, reducing senescence and restoring transdifferentiation marker expression.
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http://dx.doi.org/10.1183/23120541.00138-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911923PMC
October 2019

Use of low field nuclear magnetic resonance to monitor lung inflammation and the amount of pathological components in the sputum of cystic fibrosis patients.

Magn Reson Med 2020 07 1;84(1):427-436. Epub 2019 Dec 1.

Department of Engineering and Architecture, University of Trieste, Trieste, Italy.

Purpose: To develop a novel approach to monitor lung ventilation/inflammation in cystic fibrosis (CF) patients. Lung assessment in CF patients is relevant given that most patients succumb to respiratory failure. Respiratory functional tests (forced expiratory volume in the first second; FEV ) and inflammatory markers are used to test pulmonary ventilation/inflammation, respectively. However, FEV is effort dependent and might be uncomfortable for CF patients. Furthermore, inflammatory marker detection is costly and not rapid. To overcome these limitations, we propose the measurement, by means of low field nuclear magnetic resonance, of the spin-spin relaxation time (T ) of water hydrogens present in CF patient sputum. In CF sputum, different biological components are pathologically increased and inversely related to lung functionality. Moreover, we showed that these components alter in a dose-dependent manner the T in synthetic CF sputum.

Methods: Sputum samples were obtained from 42 CF subjects by voluntary expectoration; FEV , C-reactive protein (CRP), blood neutrophil counts together with cytokine (tumor necrosis factor alpha [TNFα], interleukin [IL]-1β, IL-4, and vascular endothelial growth factor) quantifications were then evaluated.

Results: In sputum samples, we observe that T directly correlates (r = 0.44; P < 10 ; 169 samples) with FEV . Moreover, T inversely correlates with the circulating inflammation markers CRP/neutrophil number (r = -0.44, P < 10 ; r = -0.37, P < 2 * 10 ; 103 and 86 samples, respectively) and with the sputum inflammatory cytokines TNFα/IL-β1 (r = -0.72, P < 10 ; r = -0.685, P < 10 ; 27 samples). T variations also correspond to FEV values over time in defined patients.

Conclusion: These findings, together with the fast, reliable, and simple determination of T , make our approach a novel tool potentially usable in the real world of CF patients.
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http://dx.doi.org/10.1002/mrm.28115DOI Listing
July 2020

Imaging Review of the Lung Parenchymal Complications in Patients with IPF.

Medicina (Kaunas) 2019 Sep 20;55(10). Epub 2019 Sep 20.

Department of Radiology, Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), 34100 Trieste, Italy.

Idiopathic pulmonary fibrosis (IPF) is a chronic, pulmonary-limited, interstitial lung disease with a poor prognosis. This condition is characterized by different clinical scenarios, ranging from the most typical slow and progressive deterioration of symptoms to a rapid and abrupt decline of lung function. Rapid worsening of clinical course is due to superimposed complications and comorbidities that can develop in IPF patients, with a higher incidence rate compared to the general population. These conditions may require a different management of the patient and a therapy adjustment, and thus it is fundamental to recognize them. High Resolution Computed Tomography (HRCT) is sensitive, but not specific, in detecting these complications, and can evaluate the presence of radiological variations when previous examinations are available; it recognizes ground glass opacities or consolidation that can be related to a large spectrum of comorbidities, such as infection, lung cancer, or acute exacerbation. To reach the final diagnosis, a multidisciplinary discussion is required, particularly when the clinical context is related to imaging findings.
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http://dx.doi.org/10.3390/medicina55100613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844120PMC
September 2019

Epithelial⁻Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis.

Medicina (Kaunas) 2019 Mar 28;55(4). Epub 2019 Mar 28.

Pulmonology Department, University Hospital of Cattinara, 34149 Trieste, Italy.

Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial⁻mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.
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http://dx.doi.org/10.3390/medicina55040083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524028PMC
March 2019

Is early detection of late-onset Pompe disease a pneumologist's affair? A lesson from an Italian screening study.

Orphanet J Rare Dis 2019 03 4;14(1):62. Epub 2019 Mar 4.

Respiratory Pathophysiology and Intensive Care Unit, Department of Cardio-Thoracic, University-City Hospital of Padova, Padova, Italy.

Background: Late-onset Pompe disease (LOPD) is a recessive disease caused by α-glucosidase (GAA) deficiency, leading to progressive muscle weakness and/or respiratory failure in children and adults. Respiratory derangement can be the first indication of LOPD, but the diagnosis may be difficult for pneumologists. We hypothesize that assessing the GAA activity in suspected patients by a dried blood spot (DBS) may help the diagnosis of LOPD in the pneumological setting.

Population And Methods: We performed a multicenter DBS survey of patients with suspected LOPD according to a predefined clinical algorithm. From February 2015 to December 2017, 140 patients (57 ± 16 yrs., 80 males) were recruited in 19 Italian pneumological units. The DBS test was performed by a drop of blood collected on absorbent paper. Patients with GAA activity < 2.6 μmol/L/h were considered positive. A second DBS test was performed in the patients positive to the first assay. Patients testing positive at the re-test underwent a skeletal muscle biopsy to determine the GAA enzymatic activity.

Results: 75 recruited subjects had outpatient access, 65 subjects were admitted for an acute respiratory failure episode. Two patients tested positive in both the first and second DBS test (1.4% prevalence), and the LOPD diagnosis was confirmed through histology, with patients demonstrating a deficient GAA muscle activity (3.6 and 9.1 pmol/min/mg). A further five subjects were positive in the first DBS test but were not confirmed at re-test. The two positive cases were both diagnosed after hospitalization for acute respiratory failure and need of noninvasive ventilation. Most of the recruited patients had reduced maximal respiratory pressures (MIP 50 ± 27% and MEP 55 ± 27% predicted), restrictive pattern (FEV/FVC 81.3 ± 13.6) and hypoxaemia (PaO 70.9 ± 14.5 mmHg). Respiratory symptoms were present in all the patients, but only 48.6% of them showed muscle weakness in the pelvic girdle and/or in the scapular girdle (35.7%).

Conclusions: DBS GAA activity test may be a powerful screening tool among pneumologists, particularly in the acute setting. A simple clinical algorithm may aid in the selection of patients on which to administer the DBS test.
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http://dx.doi.org/10.1186/s13023-019-1037-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399888PMC
March 2019

The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone.

Clin Respir J 2019 Mar;13(3):166-173

Department of Clinical and Biological Sciences, Interstitial and Rare Lung Disease Unit AOU San Luigi Gonzaga, Orbassano, University of Turin, Turin, Italy.

Introduction: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients.

Objective: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone.

Methods: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination.

Results And Conclusion: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95).
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http://dx.doi.org/10.1111/crj.12999DOI Listing
March 2019

Acute respiratory distress syndrome.

Eur Respir Rev 2017 Jun 26;26(144). Epub 2017 Apr 26.

Pulmonology Dept, University Hospital of Cattinara, Trieste, Italy.

Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care.
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http://dx.doi.org/10.1183/16000617.0116-2016DOI Listing
June 2017

Keratin14 mRNA expression in human pneumocytes during quiescence, repair and disease.

PLoS One 2017 15;12(2):e0172130. Epub 2017 Feb 15.

Molecular Pathology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.

The lung alveoli slowly self-renew pneumocytes, but their facultative regeneration capacity is rapidly efficient after an injury, so fibrosis infrequently occurs. We recently observed Keratin 14 (KRT14) expression during diffuse alveolar damage (DAD), but not in controls. We wonder if KRT14 may be a marker of pneumocyte transition from quiescence to regeneration. Quantitative PCR and Western blot analyses highlighted the presence of KRT14 (mRNA and protein) only in human lung samples with DAD or interstitial lung disease (ILD). In the exponentially growing cell lines A549 and H441, the mRNA and protein levels of KRT14 peaked at day one after cell seeding and decreased at day two, opposite to what observed for the proliferation marker E2F1. The inverse relation of KRT14 versus E2F1 expression holds true also for other proliferative markers, such as cyclin E1 and cyclin D1. Of interest, we also found that E2F1 silencing caused cell cycle arrest and increased KRT14 expression, whilst E2F1 stimulation induced cell cycle progression and decreased KRT14. KRT14 also increased in proliferative pneumocytes (HPAEpiC) just before transdifferentiation. Overall, our results suggest that KRT14 is a viable biomarker of pneumocyte activation, and repair/regeneration. The involvement of KRT14 in regenerative process may suggest a novel pharmaceutical target to accelerate lung repair.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172130PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310884PMC
August 2017