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Occupational hypersensitivity pneumonitis (OHP) is an interstitial lung disease caused by sensitization to an inhaled antigen. Polyethylene terephthalate (PET) is mainly used for disposable beverage bottles. A clinical case of hypersensitivity pneumonitis (HP) in a 66-year-old patient in the follow-up as a worker formerly exposed to asbestos is presented. At the first visit in 2012 a diagnosis of asbestosis and pleural plaques was formulated. In 2017 the high resolution computed tomography was performed demonstrating a slight progression of the pulmonary fibrosis, while physical examinations revealed inspiratory crackles on auscultation, and lung function tests showed a decreased diffusing capacity for carbon monoxide. The radiological and histological pictures were compatible with HP. From 1992 to 2013 the patient worked in a chemical company that produced PET for disposable beverage bottles. A diagnosis of OHP was made, and the most likely causative agents were terephthalic acid and dimethyl terephthalate. To the best of the authors' knowledge, this is the first report of an OHP case in PET production. Int J Occup Med Environ Health. 2020;33(1):119-23.

Lung Cancer (LC) is the first cause of death worldwide. Recently increased interest in interstitial lung diseases (ILD) has highlighted an association with lung cancer, offering interesting insights into the pathogenesis of the latter. Describe the association between lung cancer and ILD and evaluate the impact of LC on survival in these populations. We collected clinical, radiological, histologic data of 53 cases of advanced pulmonary fibrosis with lung cancer: 17 with UIP pattern (usual interstitial pneumonia, UIP/IPF-LC) and 36 with non-UIP pattern (ILD-LC). Adenocarcinoma was the most frequent histological subtype of lung cancer in all three groups and in UIP/IPF-LC developed in the lung periphery and in an advanced fibrosis context. Patients with DLCO%

Background The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) guidelines has some shortcomings. The aim of the present study was to develop a novel software, “IPFdatabase”, that could readily apply the diagnostic criteria per IPF guidelines and make a ‘virtual’ diagnosis of IPF. Methods Software was developed as a step-by-step compilation of necessary information according to guidelines to enable a diagnosis of IPF. Software accuracy was validated primarily by comparing software diagnoses to those previously made at a Center for Interstitial Lung Diseases. Results Clinical validation on 98 patients (68 male, age 61.0 ± 8.5 years), revealed high software accuracy for IPF diagnosis when compared to historical diagnoses (sensitivity 95.5%, specificity 96.2%; positive predictive value 95.5%, negative predictive value 96.2%). A general radiologist and a general pathologist reviewed relevant data with and without the new software: interobserver agreement increased when they used the IPFdatabase (kappa 0.18 to 0.64 for radiology, 0.13 to 0.59 for pathology). Conclusion IPFdatabase is a useful diagnostic tool for typical cases of IPF, and potentially restricts the need for MDDs to atypical and complex cases. We propose this web-designed software for instant accurate diagnosis of IPF by virtual means and for educational purposes; the software is readily accessed with mobile apps, allows incorporation of updated version of guidelines, can be utilized for gathering data useful for future studies and give physicians rapid feedback in daily practice.

Background: Serum Amyloid A (SAA) is an acute phase protein and we analyzed its concentrations in lung transplantated patients (LTX). Methods: 26 LTX patients (58.6 ± 11 years) and 11 healthy controls (55 ± 11.3 years). Three groups of LTX patients: acute rejection (AR, 7) bronchiolitis obliterans syndrome (BOS, 3), acute infection (INF, 9) and stable patients (NEG, 7). Results: In LTX patients SAA concentrations were significantly increased, particularly in AR and INF. In LTX-AR patients were observed a correlation between SAA levels and peripheral CD4+ lymphocyte percentage (r=0.9, p

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease characterized by the fibrotic thickening of subpleural and parenchymal areas of the upper lobes. It may be both idiopathic or secondary to infections, interstitial lung diseases and/or drug exposure. Often PPFE patients report recurrent lower respiratory tract infections, suggesting that repeated inflammatory alterations induced by pulmonary infections may contribute to the development/progression of PPFE.Here, we report for the first time the case of a patient affected by Giant cell Arteritis with histologically proven PPFE. The lung involvement in GCA is rare and interstitial lung diseases are usually reported as an uncommon clinical manifestation of GCA. Our patient is probably the first case presenting PPFE associated with GCA and we wonder if this is a real associative disease or a coincidence perhaps, secondary to drug effects. Keywords: Pleuroparenchymal fibroelastosis, Giant cell arteritis, Diagnosis

Pleural plaques (PPs) represent the most common non malignant asbestos-related disease. Currently PPs are widely referred as a marker of asbestos exposure and not as an independent risk factor for the development of asbestos-related neoplastic diseases (1). However, the association between PPs and pleural mesothelioma (PM) remains controversial, as some studies on cohorts of asbestos exposed workers have shown correlation between PPs and PM. Despite this, scientific literature is poor. Research has been focused on the relationship between PPs and lung cancer, while there is a lack of studies on the possible relationship between PPs and the development of PM. Case presentation A clinical case of a patient affected by asbestosis and PPs with a history of occupational asbestos exposure is presented. During the follow up a PM was diagnosed at a PP. Conclusions The widespread belief that there is no relationship between PPs and PM is not supported by a vast literature as it happens for the absence of association between PPs and lung cancer. In the patient described it is not possible to determine whether the localization of the PM at a PP is incidental or not and whether the PM can be attributed only to intense exposure or even to the presence of PPs. Similar cases may not be uncommon even if not reported in the literature. References . Maxim LD, Niebo R, Utell MJ. Are pleural plaques an appropriate endpoint for risk analyses?Inhalation Toxicology2015;27:321–334. . Pairon JC, Laurent F, Rinaldo M, Clin B, Andujar P, et al. Pleural plaques and the risk of pleural mesothelioma. JNCI2013;105:293–301. doi:10.1093/jnci/djs513

Pleuroparenchymal fibroelastosis is a rare form of upper-lobe-dominant progressive pulmonary fibrosis characterized histologically by visceral pleural thickening with collagenous fibrosis, subpleural elastosis, and intra-alveolar collagenous fibrosis. It was first described 25 years ago by Amitani et al. This report firstly describes a new variant or rare phenotype of PPFE with airway involvement, minimal pleuroparenchymal connections, and non-necrotizing granulomas.

Purpose: Diagnosing usual interstitial pneumonia (UIP) with chest CT is fundamental because of the new treatment options that could modify the prognosis of this disease. The aim of this work was to investigate the possibility of volume texture analysis (TA) in differentiating UIP from non UIP fibrosis, comparing TA parameters with histological specimens. Methods and Subjects: We selected the pre-transplant chest CTs of 61 patients (48 males); twenty-six of them (42.6%) suffered from UIP. The lung was segmented into three regions of interest (ROI), the apex (A-ROI), the middle (MD-ROI) and the lower lobe region (B-ROI), using the lung autosegmentation of the FocalPro software, Elekta ©. ROIs were analysed and TA parameters extracted and correlated with the diagnosis, by univariate and multivariate analysis; they were then tested for correlation each other, and when it was larger than 0.80, the variable with the lowest univariable correlation was omitted. Results: Only B-ROI TA parameters resulted significantly correlated with the diagnosis in univariate analysis (Skewness (p:0.041), Kurtosis (p:0.009), Entropy (p:0.026), grey-level co-occurrence matrix (GLCM) Homogeneity (p:0.024), GLCM Contrast (p:0.001), GLCM Entropy (p:0.014), GLCM Dissimilarity (p:0.001), Contrast (p:0.003), SZE (p:0.023) and zone percentage (ZP) (p:0.007)). Skewness, entropy, GLCM Homogeneity and Entropy, and ZP were excluded because of the correlation larger than 0.80. Logistic regression underlined a significant result for GLCM Dissimilarity (p:0.003), with an overall R2 of 0.219 and an AUC of 0.719. Conclusion: Volumetric TA seems to improve the differential diagnosis of pulmonary fibrosis.

Background The aim of this study was to assess the prognostic significance of Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after induction chemotherapy in surgically resected IIIA-N2 patients. Methods Between January 2002 and November 2008, we reviewed 50 consecutive patients (39 males) with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who underwent radical resection following induction chemotherapy. Five-year survival in the series was evaluated in relation to lymph node downstaging, histology, extent of resection, number of chemotherapy cycles, pT status, sex and age. It was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib 1 expression), dividing the patients into two groups according to whether they were above or below the 50th percentile for each parameter. The associations between mortality and the abovementioned prognostic factors were explored using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. Results The monovariate analysis confirmed the positive prognostic role of lymph node downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1 expression under the 50th percentile were also associated with better 5-yr survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither apoptosis nor the other prognostic factors showed any statistical impact on long-term survival. The multivariate analysis showed Mi to be an independent prognostic factor (P=0.005). Conclusions Although lymph node downstaging has been considered the principal prognostic factor after induction chemotherapy and surgical resection, Mi and Mib1 expression in residual tumor can predict long-term survival more accurately.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity and attenuation. We provide a novel RSV vaccine concept based on a genome replication-deficient Sendai vector that has many favorable vaccine characteristics. The specific vaccine design guarantees genetic stability of the transgene; furthermore, it supports a favorable presentation of the antigen, activating the adaptive response, features that other vectored vaccine approaches have often had difficulties with. Wide immunological and pathological analyses in mice confirmed the validity and efficacy of this approach after both parenteral and mucosal administration. Above all, this concept is suitable for initiating clinical studies, and it could also be applied to other infectious diseases.