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Background: FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF).Methods: Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted).Results: 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study.Conclusions: FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF.Trial Registration: NCT02803580. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Fibrotic idiopathic interstitial pneumonias are chronic and progressive lung diseases with different prognosis, with idiopathic pulmonary fibrosis (IPF) having the worst prognosis. Many patients need a surgical lung biopsy for the definite diagnosis of IPF but age and the clinical context often contraindicate this procedure. The aim of this study is to identify predictors of survival, apart from lung biopsy, in patients with definite and possible IPF. PATIENTs AND METHODS: We studied 42 patients with HRCT pattern of definite or possible IPF, by assessing the mortality in relationship with baseline HRCT and functional findings. HRCT was assessed both as prevalent pattern (definite vs possible UIP) and as score of the different abnormalities (in particular, honeycombing (HC) and total fibrotic score). Pulmonary function was assessed as baseline FVC, TLC and DLCO values, as well as change over 6 months of follow-up. Both univariate and multivariate analyses were performed in order to detect predictors of mortality. RESULTS: During follow-up, 10 out of 42 patients died. Mortality rate was not different according to the qualitative pattern of fibrosis at HRCT. Among the different HRCT scores, a cut-off of 15% in the HC score differentiated patients with higher mortality rate. A lower baseline FVC, and a greater decrease in pulmonary function after 6 months, were both associated with higher mortality. In a logistic analysis taking in consideration clinical, radiological and functional findings, only baseline FVC and FVC change after 6 months resulted significant predictors of mortality. CONCLUSIONS: Functional evaluation at the baseline and during follow-up is more relevant than HC score for the prognosis of patients with definite and possible IPF. [ABSTRACT FROM AUTHOR]

Twenty healthy, asymptomatic long-term cigarette smokers (8 males, 12 females; mean age: 43 +/- 9 years) were selected at random from a larger series receiving nicotine replacement therapy (NRT) for 12 weeks to study the effects of NRT on plasma markers of oxidative stress. Plasma aliquots, obtained at baseline (T0) and after 12 weeks (T12) of NRT, were used to measure malondialdeyde (MDA) and total Trolox-equivalent antioxidant capacity (TEAC). In subjects who completely quit smoking ('quitters', n = 10), MDA was higher at T0 (1.08 mumol/l, interquartile range 0.85-1.16) than at T12 (0.71 mumol/l, range 0.32-0.92; p < 0.01), and TEAC was lower at T0 (1.20 mM, range 1.11-1.31) than at T12 (1.43 mM, range 1.31-1.49; p < 0.05). In subjects who had only reduced the number of cigarettes smoked per day ('reducers', n = 10), differences between the T0 and T12 levels of MDA (0.81 [0.75-0.96] vs. 0.76 [0.58-0.84] mumol/l) and TEAC (1.28 [1.05-1.50] vs. 1.25 [1.09-1.42] mM) were not significant. At T0, MDA and cotinine levels correlated in reducers (r = 0.79, p < 0.05) and, though not significantly, in quitters (r = 0.50, p = 0.12). At T12 this relationship between MDA and cotinine was still present in the reducers (r = 0.70, p < 0.05), while the scatter of points in quitters was completely dispersed (r = (0.09). These results show that smoking cessation but not smoking reduction is associated with decreased markers of oxidative stress in the plasma of active cigarette smokers. [ABSTRACT FROM AUTHOR]

Objectives: Lung ultrasound (LUS) and high-resolution CT (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a 1 year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes., Methods: SSc-ILD patients who started NIN were enrolled and followed for 12 months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after 1 year and quantitatively analysed with CALIPER software., Results: Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after 12 months (from 175.1 [66.7] to 120.8 [70.3] for BL, P = 0.005; and from 50.6 [32.5] to 37.2 [22.4] for PLI, P = 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction in both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (P = 0.016 and P = 0.04, respectively) and Saint George's Respiratory Questionnaire (P = 0.006 and P = 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after 12 months of NIN, thus paralleling the stabilization obtained at pulmonary function tests., Conclusion: We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts., Methods: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide ( D LCO ) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups., Results: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations., Conclusion: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients., Competing Interests: Conflict of interest: J. Jacob reports fees from Boehringer Ingelheim, Roche, NHSX, Takeda and GlaxoSmithKline, unrelated to the submitted work, and was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z and the NIHR Biomedical Research Centre at University College London. N. Mogulkoc reports grant TUBITAK (EJP Rare Disease project “COCOS-IPF”), fees from Boehringer Ingelheim, Roche, and Nobel Turkey unrelated to the submitted work, and received support for travel to meetings from Roche and Actelion. T.J. Corte reports unrestricted educational grants from Boehringer Ingelheim, Roche, Biogen and Galapagos, fees from Roche, BMS, Boehringer Ingelheim, Vicore and DevPro, assistance for travel to meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board for Roche, BMS, Boehringer Ingelheim, Vicore, Ad Alta, Bridge Biotherapeutics and DevPro. P. Vasudev reports financial interests from Blackford Analysis. T. Goos is supported by Research Foundation Flanders (1S73921N). L.J. De Sadeleer is supported by Marie Sklodowska-Curie actions postdoctoral fellowship within the European Union's Horizon Europe research and innovation programme. H. Jo reports fees from Boehringer Ingelheim and Roche, and received assistance for travel to meetings from Boehringer Ingelheim and Roche. S. Verleden reports consultancy fees from Boehringer Ingelheim and Sanofi. M. Vermant is supported by an FWO (Research Flanders Foundation) fellowship. S.M. Janes reports fees from AstraZeneca, Bard1 Bioscience, Achilles Therapeutics and Jansen unrelated to the submitted work, received assistance for travel to meetings from AstraZeneca and Takeda, and is the investigator lead on grants from GRAIL Inc., GlaxoSmithKline plc and Owlstone. A.U. Wells reports personal fees and non-financial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals, and personal fees from Blade, outside of the submitted work. The remaining authors report no relevant conflicts of interest., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Objective: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects., Methods: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them., Results: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN., Conclusion: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects., (© 2023. The Author(s).)

In patients with combined pulmonary fibrosis and emphysema, emphysema and fibrosis do not have a synergistic effect that results in worsened survival when compared to IPF patients without emphysema https://bit.ly/35EJMo6., Competing Interests: Conflict of interest: A. Zhao has nothing to disclose. Conflict of interest: E. Gudmundsson has nothing to disclose. Conflict of interest: N. Mogulkoc has nothing to disclose. Conflict of interest: M.G. Jones has nothing to disclose. Conflict of interest: C. van Moorsel has nothing to disclose. Conflict of interest: T.J. Corte reports personal fees from Ad Alta, grants and personal fees from Boehringer Ingelheim and Bristol Myers Squibb, personal fees from Promedior, grants and personal fees from Roche, and grants from Actelion, Avalyn Pharma, Biogen and Galapagos, outside the submitted work. Conflict of interest: C. Romei has nothing to disclose. Conflict of interest: R. Savas has nothing to disclose. Conflict of interest: C.J. Brereton has nothing to disclose. Conflict of interest: H.W. van Es has nothing to disclose. Conflict of interest: H. Jo has nothing to disclose. Conflict of interest: A. De Liperi has nothing to disclose. Conflict of interest: O. Unat has nothing to disclose. Conflict of interest: K. Pontoppidan has nothing to disclose. Conflict of interest: F. van Beek has nothing to disclose. Conflict of interest: M. Veltkamp has nothing to disclose. Conflict of interest: P. Hopkins has nothing to disclose. Conflict of interest: Y. Moodley has nothing to disclose. Conflict of interest: A. Taliani has nothing to disclose. Conflict of interest: L. Tavanti has nothing to disclose. Conflict of interest: B. Gholipour has nothing to disclose. Conflict of interest: A. Nair reports a proportion of their permanent employment at UCL Hospital is funded by the Biomedical Research Centre, and nonfinancial support for an advisory board from Aidence BV, the Netherlands, outside the submitted work. Conflict of interest: S. Janes reports personal fees and nonfinancial support from AstraZeneca, personal fees from Bard1 Bioscience, Achilles Therapeutics and Jansen, nonfinancial support from Takeda, and grants from GRAIL Inc., GlaxoSmithKline plc and from Owlstone, outside the submitted work. Conflict of interest: I. Stewart has nothing to disclose. Conflict of interest: D. Barber has nothing to disclose. Conflict of interest: D.C. Alexander has nothing to disclose. Conflict of interest: A.U. Wells reports personal fees and nonfinancial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals, and personal fees from Blade, outside the submitted work. Conflict of interest: J. Jacob reports personal fees from Boehringer Ingelheim and Roche, grants and personal fees from GlaxoSmithKline, personal fees from NHSX, and grants from the Wellcome Trust, outside the submitted work., (Copyright ©The authors 2021.)

In this paper, we present an approach and an algorithm aimed at minimising the energy consumption of enterprise Wireless Local Area Networks (WLANs) during periods of low user activity. We act on two network management aspects: powering off some Access Points (APs), and choosing the level of transmission power of each AP. An efficient technique to allocate the user terminals to the various APs is the key to achieving this goal. The approach has been formulated as an integer programming problem with nonlinear constraints, which comes from a general but accurate characterisation of the WLAN. This general problem formulation has two implications: the formulation is widely applicable, but the nonlinearity makes it NP-hard. To solve this problem to optimality, we devised an exact algorithm based on a customised version of Benders' decomposition method. The computational results proved the ability to obtain remarkable power savings. In addition, the good performance of our algorithm in terms of solving times paves the way for its future deployment in real WLANs.

We investigated the potential role of extracellular vesicles as biomarkers in interstitial lung diseases. Endothelial derived extracellular vesicles were enumerated in 14 consecutive patients with usual interstitial pneumonia or possible usual interstitial pneumonia, and 18 normal controls by flow cytometry. The number of endothelial derived extracellular vesicles was significantly greater in patients compared to controls [160 (73) vs. 85 (31) events/min respectively; median (interquartile range); p <0.001]. A receiving operating characteristic curve shows that an arbitrary cut-off of 104 events/min corresponded to a sensitivity of 93%, and a specificity of 83%. Endothelial cell derived extracellular vesicles are potential biomarkers for the diagnosis of interstitial lung diseases., (© 2019 by the Association of Clinical Scientists, Inc.)

Rationale: Real-world data on pirfenidone treatment of patients with idiopathic pulmonary fibrosis (IPF) are limited. This study assessed the effectiveness of pirfenidone in a large real-life Italian IPF cohort., Methods: IRENE was an observational, retrospective study of patients with IPF treated with pirfenidone in routine clinical practice (18 centres). At Month 6, a mandatory re-evaluation of forced vital capacity (FVC) decline (absolute change < 10%) was required to continue pirfenidone. The primary effectiveness outcomes were absolute change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12. Safety was described by adverse event (AE) occurrence. Prespecified subgroups included sex, age, presence/absence of emphysema, usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and baseline lung function., Results: The study included 379 patients (mean age, 67.6 years; 78.1% male). Mean change from baseline in FVC and the percentage of patients with ≥ 10% absolute decline in % predicted FVC at Month 12 were -81.8 mL (SD, 419.6 mL; P = 0.002) and 16.0% (95% CI, 12.2-20.9%), respectively. Disease progression was similar across prespecified subgroups, including patients with definite vs possible UIP. Overall, 211 AEs occurred in 149 patients (39.3%), with serious AEs in 31 patients (8.2%) and 9 discontinuations due to AEs. Skin and gastrointestinal AEs were most frequent. Fifteen patients (4.0%) died., Conclusions: The decline in FVC and the safety profile observed in this real-world IPF cohort were consistent with the findings of the Phase III pirfenidone trials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Thin-slices multi-detector computed tomography (MDCT) plays a key role in the differential diagnosis of interstitial lung disease (ILD). However, thin-slices MDCT has a limited ability to detect active inflammation, which is an important target of newly developed ILD drug therapy. Magnetic resonance imaging (MRI), thanks to its multi-parameter capability, provides better tissue characterisation than thin-slices MDCT.Our aim was to summarise the current status of MRI applications in ILD and to propose an ILD-MRI protocol. A systematic literature search was conducted for relevant studies on chest MRI in patients with ILD.We retrieved 1246 papers of which 55 original papers were selected for the review. We identified 24 studies comparing image quality of thin-slices MDCT and MRI using several MRI sequences. These studies described new MRI sequences to assess ILD parenchymal abnormalities, such as honeycombing, reticulation and ground-glass opacity. Thin-slices MDCT remains superior to MRI for morphological imaging. However, recent studies with ultra-short echo-time MRI showed image quality comparable to thin-slices MDCT. Several studies demonstrated the added value of chest MRI by using functional imaging, especially to detect and quantify inflammatory changes.We concluded that chest MRI could play a role in ILD patients to differentiate inflammatory and fibrotic changes and to assess efficacy of new ILD drugs., Competing Interests: Conflict of interest: C. Romei has nothing to disclose. Conflict of interest: L. Turturici has nothing to disclose. Conflict of interest: L. Tavanti has nothing to disclose. Conflict of interest: J. Miedema has nothing to disclose. Conflict of interest: S. Fiorini has nothing to disclose. Conflict of interest: M. Marletta has nothing to disclose. Conflict of interest: P. Wielopolski has nothing to disclose. Conflict of interest: H. Tiddens reports industry funding from Roche, lecture and advisory board fees from Novartis, and grants from CFF, Vertex, Gilead and Chiesi, outside the submitted work. In addition, H. Tiddens has a patent licensed with Vectura, and a patent PRAGMA-CF scoring system issued. Conflict of interest: F. Falaschi has nothing to disclose. Conflict of interest: P. Ciet reports personal fees from Vertex Pharmaceutical, outside the submitted work., (Copyright ©ERS 2018.)

The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A 2B adenosine receptor subtype activation, too. However, the relationship between A 2B AR and EMT has not been investigated, yet. Herein, the A 2B AR characterization was carried out in human epithelial lung cells. Moreover, the effects of receptor activation on EMT were investigated in the absence and presence of transforming growth factor-beta (TGF-β1), which has been known to promote the transition. The A 2B AR activation alone decreased and increased the expression of epithelial markers (E-cadherin) and the mesenchymal one (Vimentin, N-cadherin), respectively, nevertheless a complete EMT was not observed. Surprisingly, the receptor activation counteracted the EMT induced by TGF-β1. Several intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2 phosphorylation has been demonstrated to counteract and promote the transition, respectively. The A 2B AR stimulation was able to modulated these two pathways, cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway, the A 2B AR-mediated EMT promotion were exacerbated, and conversely the selective inhibition of MAPK/ERK counteracted the receptor-induced transition. These results highlighted the A 2B AR as one of the receptors involved in the modulation of EMT process. Nevertheless, its activation is not enough to trigger a complete transition, its ability to affect different intracellular pathways could represent a mechanism at the basis of EMT maintenance/inhibition based on the extracellular microenvironment. Despite further investigations are needed, herein for the first time the A 2B AR has been related to the EMT process, and therefore to the different EMT-related pathologies.

Purpose: The objective of the study was to determine whether HRCT criteria for Usual Interstitial Pneumonia (UIP), possible UIP or no-UIP pattern recommended by ATS/ERS/JRS/ALAT guidelines 2011 are able to predict progression and prognosis of the disease in a group of patients with fibrotic idiopathic interstitial pneumonia (IIP)., Materials and Methods: This was a retrospective study conducted with the approval of the ethics committee. Two radiologists at baseline HRCT distributed 70 patients with fibrotic IIP into three groups on the basis of the 2011 guidelines: UIP pattern (group 1), possible UIP pattern (group 2), inconsistent with UIP pattern (group 3). The different abnormalities (honeycombing, reticulation, ground-glass and traction bronchiectasis), fibrotic score (reticulation + honeycombing) and overall CT score were visually scored at baseline and during the follow-up (total HRCT 178). The mortality rate of the three groups was compared. The baseline abnormalities were then correlated with the mortality rate in the UIP group., Results: The inter-observer agreement in the classification of the abnormalities in the three groups was almost perfect (k = 0.92). After consensus, 44 patients were classified into group 1, 13 into group 2 and 13 into group 3. During a mean follow-up of 1386 days, overall CT score, fibrotic score, honeycombing and traction bronchiectasis showed a significant progression in group 1. The mortality rate was significantly higher in group 1 (18 deaths) versus group 2 and 3 (1 death each). In group 1, baseline honeycombing rate higher than 25 %, fibrotic score higher than 30, overall CT score greater than 45 and traction bronchiectasis in more than 4 lobes defined the worst prognosis., Conclusion: HRCT classification based on 2011 guidelines showed high accuracy in stratifying fibrotic changes because in our study UIP, possible UIP and inconsistent with UIP pattern seem to be correlated with different disease progression and mortality rate.

Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons). Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations). Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor without affecting tissue factor mRNA. Procoagulant microparticles are increased in interstitial lung diseases and correlate with functional impairment. These structures might contribute to the activation of factor X and to the factor Xa-mediated fibrotic response in lung injury.

Healthcare workers (HCW) are exposed to many different pathogens, and cases of occupational infection have been reported involving the vast majority of known and emerging agents. The risk is present during all the phases of patient care and manipulation of biologic materials, and the implementation of Standard Precautions--and biosafety level 2 measures in the laboratory--and Transmission-Based Precautions in all health settings represents the necessary preventive intervention required by law. Percutaneous exposures represent an extremely frequent event in healthcare facilities; among the many pathogens acquired through this type of exposure, those of highest concern due to the frequency of exposure are HIV, HBV and HCV. Over the last 10 years, though the risk of exposure is still not negligible, occupational infection with HBV has become a rare event; conversely, the incidence of acute C hepatitis became significantly higher among HCW (1,6 per 100.000 inhabitants) with respect to the general population (0,6), with a seroconversion rate following an occupational exposure between 0,5% and 1,8%; finally, reports of occupational HIV infection have decreased, probably also as a secondary beneficial effect of antiretroviral treatment in patients and post-exposure prophylaxis in HCW. The Studio Italiano Rischio Occupazionale da HIV (SIROH) documented from 1986 to 2009 one occupational HBV case, 6 HIV cases (the last one in 2007) and 32 HCV cases. In Europe, the Directive 2010/32/EU approved on May 10 2010 requires Member State to implement within three years a global strategy to prevent occupational exposures in the healthcare setting, particularly with respect to needlestick and sharp injuries, including the adoption, based on risk assessment, of devices incorporating safety features. In Italy the introduction of these devices, according to data collected by the SIROH, showed the possibility to decrease percutaneous exposures by 75%, an effect sustained over time if supported by information, education and training.