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Introduction Timely and accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is challenging, requiring specific tests including chest high-resolution computed tomography (HRCT), and limited by access to specialist centres with a multidisciplinary team (MDT). Here we describe PerFECT 2.0, an Italian web-based platform designed to create a network between tertiary centres with an MDT (hubs) and secondary centres (spokes), aiming to facilitate the diagnosis of IPF. Methods PerFECT 2.0 went live on 1 November 2016. Spoke centres submit anonymised documentation (HRCT images, pathological samples, clinical data) for a second opinion on the potential diagnosis of IPF from a hub centre. HRCT images are quickly uploaded, with patient-identifying information automatically removed. The hub centre views documentation online (no downloads allowed), makes any further information requests, then returns their second opinion as free text. An e-learning area contains educational material and simulated training clinical cases. Metrics were collected for 2017–2019; a user survey was conducted from 30 June–31 July 2020. Results Ten hub centres and 137 spoke centres have registered. The requests for a second opinion numbered 251 in 2017, 270 in 2018 and 265 in 2019 (overall mean 19.9 requests per month). The proportion of requests answered was 100.0% (251) in 2017, 100.0% (270) in 2018 and 97.7% (259) in 2019. The mean response time was 15.7 days. In the user survey, of nine hub responders and 19 spoke responders, 78% and 74%, respectively, reported that the platform is easy to use, and 100% and 89%, respectively, would recommend the platform to colleagues. Conclusion The PerFECT 2.0 web-based platform has created a network that enables secondary centres to gain quick and easy access to a second opinion from a tertiary centre with an MDT through online evaluation of anonymised documentation, thereby facilitating and supporting the timely and accurate diagnosis of IPF. Supplementary Information The online version contains supplementary material available at 10.1007/s41030-021-00155-8.

Background Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW P P P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (P = 0.01)]. Conclusions Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Background Comorbidities are common in interstitial lung diseases (ILD) and have an important association with survival, but the frequency and prognostic impact of comorbidities in unclassifiable interstitial lung disease (uILD) remains elusive. We aimed to describe the prevalence of comorbidities and assess the impact on survival in patients with uILD. Furthermore, we aimed to identify and characterize potential phenotypes based on clusters of comorbidities and examine their association with disease progression and survival. Methods Incident patients diagnosed with uILD were identified at two ILD referral centers in Denmark and Germany from 2003 to 2018. The diagnosis uILD was based on multidisciplinary team meetings. Clinical characteristics and comorbidities were extracted from ILD registries and patient case files. Survival analyses were performed using Cox regression analyses, disease progression was analyzed by linear mixed effects models, and clusters of comorbidities were analyzed using self-organizing maps. Results A total of 249 patients with uILD were identified. The cohort was dominated by males (60%), former (49%) or current (15%) smokers, median age was 70 years, mean FVC was 75.9% predicted, and mean DLCO was 49.9% predicted. One-year survival was 89% and three-year survival was 73%. Eighty-five percent of the patients had ≥ 1 comorbidities, 33% had ≥ 3 comorbidities and 9% had ≥ 5 comorbidities. The only comorbidity associated with excess mortality was dyslipidemia. No association between survival and number of comorbidities or the Charlson comorbidity index was observed. Three clusters with different comorbidities profiles and clinical characteristics were identified. A significant annual decline in FVC and DLCO % predicted was observed in cluster 1 and 2, but not in cluster 3. No difference in mortality was observed between the clusters. Conclusions The comorbidity burden in uILD is lower than reported in other types of ILD and the impact of comorbidities on mortality needs further clarification. Three clusters with distinct comorbidity profiles were identified and could represent specific phenotypes. No difference in mortality was observed between clusters, but slower disease progression was observed in cluster 3. Better understanding of disease behavior and mortality will require further studies of subgroups of uILD with longer observation time.

Introduction: Severe morning stiffness with painful involvement of the girdles are often referred by patients with Interstitial Lung Disease (ILD), but the association between ILD and Polymyalgia Rheumatica (PMR) is rarely reported. The purpose of the work is to describe a series of patients classified as having PMR with ILD. Material and methods: We retrospectively enrolled patients with a diagnosis of PMR referred to our center during the previous year for respiratory symptoms. Data concerning clinical and serological manifestations suggesting Connective Tissue Disease (CTD), High-Resolution Chest Tomography (HRCT), and Pulmonary Function Tests (PFTs) were systematically collected in order to verify the diagnosis. Results: Fifteen out of seventeen PMR patients had ILD. Ten patients had a confirmed diagnosis of PMR, while in five patients a CTD was discovered. Seven patients showed a severe restrictive pattern at PFTs requiring oxygen supplementation (five with PMR and two with CTD). In thirteen patients pulmonary symptoms started before or together with muscular symptoms. Regarding HRCT patterns, patients showed a Nonspecific Interstitial Pneumonia in nine cases, Usual Interstitial Pneumonia (UIP) and possible UIP in two and three cases, and a single case of Organizing Pneumonia and Combined Pulmonary Fibrosis and Emphysema Syndrome. Conclusions: Lung involvement should be evaluated in PMR patients, especially if asthenia is poorly responsive to low doses of steroids. In these cases, the diagnosis should be re-evaluated in depth, looking for a seronegative Rheumatoid Arthritis, a clinically amyopathic myositis or Interstitial Pneumonia with Autoimmune features. Keywords: Interstitial lung disease, Polymyalgia rheumatica, Connective tissue disease, Antisynthetase syndrome, Myositis, Interstitial pneumonia with autoimmune features

Background The assessment of Idiopathic Pulmonary Fibrosis (IPF) using HRCT requires great experience and is limited by a significant inter-observer variability, even between trained radiologists. The evaluation of HRCT through automated quantitative analysis may hopefully solve this problem. The accuracy of CT-histogram derived indexes in the assessment of survival in IPF patients has been poorly studied. Methods Forty-two patients with a diagnosis of IPF and a follow up time of 3 years were retrospectively collected; HRCT and Pulmonary Function Tests (PFTs) performed at diagnosis time were analysed; the extent of fibrotic disease was quantified on HRCT using kurtosis, skewness, Mean Lung Density (MLD), High attenuation areas (HAA%) and Fibrotic Areas (FA%). Univariate Cox regression was performed to assess hazard ratios for the explored variables and a multivariate model considering skewness, FVC, DLCO and age was created to test their prognostic value in assessing survival. Through ROC analysis, threshold values demonstrating the best sensitivity and specificity in predicting mortality were identified. They were used as cut-off points to graph Kaplan-Meier curves specific for the CT-indexes. Results Kurtosis, skewness, MLD, HAA% and FA% were good predictors of mortality (HR 0.44, 0.74, 1.01, 1.12, 1.06; p = 0.03, p = 0.01, p = 0.02, p = 0.02 and p = 0.017 respectively). Skewness demonstrated the lowest Akaike’s information criterion value (55.52), proving to be the best CT variable for prediction of mortality. Significant survival differences considering proposed cut-off points were also demonstrated according to kurtosis (p = 0.02), skewness (p = 0.005), MLD (p = 0.003), HAA% (p = 0.009) and FA% (p = 0.02) – obtained from quantitative HRCT analysis at diagnosis time. Conclusions CT-histogram derived indexes may provide an accurate estimation of survival in IPF patients. They demonstrate a correlation with PFTs, highlighting their possible use in clinical practice.

Background: Progressive hypoxemia is a hallmark of fibrosing interstitial lung disease (fILD). OxyHem is a simple-to-measure correlate of oxygen content. We aimed to assess whether OxyHem correlates with outcomes in fILD. Methods: The database of our center was reviewed for fILDs. OxyHem (g/dL) was calculated as Hb x fractional SaO2. Clinical and functional data with absolute declines of FVC≥10% and/or DLCO≥15% were retrospectively analysed. Predictive values were evaluated by binary logistic and Cox regression analyses with age, gender, BMI, DLCO and FVC as covariates. Results:650 fILD patients (29% IPF, 28.6% cHP, 12.4% iNSIP, 16.3% uILD, 9.2% RA-ILD, 4.3% other ILD; 63.3% male, mean age 68.4 years) were analysed. The mean follow-up period was 16.8 months. Mean FVC was 74.4%pred., and 29.3% of patients showed a FVC decline ≥10%. OxyHem (mean13.4±1.4 g/dL) was strongly related to FVC decline ≥10% (odds ratio 1.33, p=0.0002) and also an independent predictor of the first occurrence of FVC decline ≥10% (hazards ratio [HR] 1.53, p=0.003). No similar relationships were observed for DLCO decline. Mortality was analysed in the IPF subgroup, in which 31/187 patients (16.4%) died. OxyHem Conclusion: OxyHem is an independent predictor of disease progression and outcomes in fILD. Future work has to validate these findings in larger cohorts.

Background: Fibrosing interstitial lung diseases other than IPF can develop a progressive phenotype (PF-ILD). While recent clinical trials have gained significant insights into management aspects for PF-ILD, different definitions were applied. We therefore aimed to compare patient cohorts according to these definitions and associated outcomes Methods: 587 fILDs with a follow up > 24 months were identified at our tertiary ILD referral Center. Patient characteristics and outcomes were assessed retrospectively and categorized as PF-ILD according to INBUILD (IN), RELIEF (RE) and Cottin (CO; ERR 2018). Results: Patients had HP (39%), iNSIP (13%), uILD (22%), CTD-ILD (24%), and others (1%). 53.4% were male, mean age 65±11.8 years, mean FVC% 72.8±2, mean DLCO% 47.3±1. The percentage of PF-ILD differed according to the 3 criteria (CO, RE, IN) (41%, 32%, 48%, fig). Acute exacerbations occurred more frequently in PF-ILD (25.6%, 23.9%, 24.9%) than in non PF-ILD (p 12 months while RELIEF identified a worse cohort. Conclusions: This study reveals that the categorization as PF-ILD differs between definitions which has important prognostic and therapeutic implications. Prospective studies are needed to confirm these results and international accepted criteria for PF-ILD have to be defined.

This study aims to assess the peripheral blood cell count &ldquo, signature&rdquo, of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) to discriminate promptly between COronaVIrus Disease 19 (COVID-19) and community-acquired pneumonia (CAP). We designed a retrospective case-control study, enrolling 525 patients (283 COVID-19 and 242 with CAP). All patients had a fever and at least one of the following signs: cough, chest pain, or dyspnea. We excluded patients treated with immunosuppressants, steroids, or affected by diseases known to modify blood cell count. COVID-19 patients showed a significant reduction in white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and platelets. We studied these parameters univariately, combined the significant ones in a multivariate model (AUROC 0.86, Nagelkerke PSEUDO-R2 0.5, Hosmer&ndash, Lemeshow p-value 0.9) and examined its discriminative performance in an internally-randomized validation cohort (AUROC 0.84). The cut-off selected according to Youden&rsquo, s Index (&minus, 0.13) showed a sensitivity of 84% and a specificity of 72% in the training cohort, and a sensitivity of 88% and a specificity of 73% in the validation cohort. In addition, we determined the probability of having COVID-19 pneumonia for each Model for possible Early COvid-19 Recognition (MECOR) Score value. In conclusion, our model could provide a simple, rapid, and cheap tool for prompt COVID-19 diagnostic triage in patients with CAP. The actual effectiveness should be evaluated in further, prospective studies also involving COVID-19 patients with negative nasopharyngeal swabs.

Background: Our study assesses the diagnostic value of different features extracted from high resolution computed tomography (HRCT) images of patients with idiopathic pulmonary fibrosis. These features are investigated over a range of HRCT lung volume measurements (in Hounsfield Units) for which no prior study has yet been published. In particular, we provide a comparison of their diagnostic value at different Hounsfield Unit (HU) thresholds, including corresponding pulmonary functional tests. Methods: We consider thirty-two patients retrospectively for whom both HRCT examinations and spirometry tests were available. First, we analyse the HRCT histogram to extract quantitative lung fibrosis features. Next, we evaluate the relationship between pulmonary function and the HRCT features at selected HU thresholds, namely &minus, 200 HU, 0 HU, and +200 HU. We model the relationship using a Poisson approximation to identify the measure with the highest log-likelihood. Results: Our Poisson models reveal no difference at the &minus, 200 and 0 HU thresholds. However, inferential conclusions change at the +200 HU threshold. Among the HRCT features considered, the percentage of normally attenuated lung at &minus, 200 HU shows the most significant diagnostic utility. Conclusions: The percentage of normally attenuated lung can be used together with qualitative HRCT assessment and pulmonary function tests to enhance the idiopathic pulmonary fibrosis (IPF) diagnostic process.

Interstitial Lung Diseases (ILDs) represent a heterogeneous group of pathologies, which may be related to different causes. A low percentage of these lung diseases may be secondary to the administration of drugs or substances. Through the PubMed database, an extensive search was performed in the fields of drug toxicity and interstitial lung disease. We have evaluated the different classes of drugs associated with pulmonary toxicity. Several different high resolution computed tomography (HRCT) patterns related to pulmonary drug toxicity have been reported in literature, and the most frequent ILDs patterns reported include Nonspecific Interstitial Pneumonia (NSIP), Usual Interstitial Pneumonia (UIP), Hypersensitivity Pneumonitis (HP), Organizing Pneumonia (OP), Acute Respiratory Distress Syndrome (ARDS), and Diffuse Alveolar Damage (DAD). Finally, from the electronic database of our Institute we have selected and commented on some cases of drug-induced lung diseases related to the administration of common drugs. As the imaging patterns are rarely specific, an accurate evaluation of the clinical history is required and a multidisciplinary approach—involving pneumologists, cardiologists, radiologists, pathologists, and rheumatologists—is recommended.

To evaluate the radiological findings in patients with cryptogenic organizing pneumonia (COP) before steroid treatment and their behavior after therapy, we retrospectively evaluated a total of 22 patients with a diagnosis of COP made by bronchoalveolar lavage (BAL), biopsy or clinical/radiological features, and the patients were followed between 2014 and 2018 at the hospital, the demographic data, symptoms, radiologic findings, diagnostic methods and treatment plans of patients were collected from patients&rsquo, hospital records. At least two CT scans of 22 patients (16 female and six men) were evaluated, the first one before starting steroid therapy and the others after therapy. At baseline CT scans, the most common radiological finding was the presence of consolidations (18/22 patients, 81.8%), ground-glass opacities were also very common (15/25, 68.1%). The other findings were as follows: nodules and masses (5/22, 22.7%), atoll sign (4/22, 18.1%), perilobular pattern (3/22, 13.6%) and parenchymal bands (3/22, 13.6%). Two patients had a significant relapse after reducing/interrupting therapy, while three had a complete resolution and are not currently under therapy (maintenance of clinical remission with no oral corticosteroid (OCS)). In High-resolution computed tomography (HRCT) scans after therapy, consolidations were still observable in seven patients (five in new areas of the lung-migratory infiltrates), while most of them disappeared, leaving a residual area of ground glass opacity in two patients. One patient had a residual of the perilobular pattern, with the disappearing of the other findings (consolidations and ground-glass opacities). Two patients developed a fibrosing pattern despite the therapy (9.5%). Cryptogenic organizing pneumonia tends to respond to oral corticosteroid treatment, but some patients may have a null or partial response. We highlight the behavior of this disease after proper therapy.

Purpose The purpose of this study was to investigate histogram-based quantitative high-resolution computed tomography (HRCT) indexes in the assessment of lung cancer (LC) development in idiopathic pulmonary fibrosis (IPF) patients. Materials and methods From IPF databases of 2 national respiratory centers, we retrospectively studied patients with and without LC development-respectively, divided into Group A (n=16) and Group B (n=33). The extent of fibrotic disease was quantified on baseline and follow-up HRCT examinations using kurtosis, skewness, percentage of high attenuation area (HAA%), and percentage of fibrotic area (FA%). These indexes were compared between the 2 groups using the Mann-Whitney U test. In the prediction of LC development, receiver operating characteristic analysis was performed to assess threshold values of HRCT indexes. Results At baseline, no difference was reported among groups for kurtosis, skewness, HAA%, and FA%, with P-values of 0.0881, 0.0606, 0.0578, and 0.0606, respectively. On follow-up, significant differences were reported, with P-values of 0.0174 for kurtosis, 0.0313 for skewness, 0.0297 for HAA%, and 0.0407 for FA%.On baseline HRCT, in the prediction of LC development, receiver operating characteristic analysis reported sensibility and specificity of 87.5% and 45.45% for kurtosis, 68.75% and 63.64% for skewness, 81.25% and 54.55% for FA%, and 75% and 60.61% for HAA%. Conclusions LC development is associated with progression of fibrosis; at baseline, FA% and HAA% reported more convenient sensitivity/specificity ratios in the prediction of LC development.

The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases. This review describes how the nintedanib clinical programme has helped to address some of these challenges. Data from this programme have informed changes to the IPF diagnostic guidelines, the timing of treatment initiation, and the assessment of disease progression. The use of nintedanib to treat patients with advanced lung function impairment, concomitant emphysema, patients awaiting lung transplantation and patients with IPF and lung cancer is discussed. The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and other progressive fibrosing interstitial lung diseases, are described. Further developments in these areas should continue to improve patient outcomes, The page processing charges for this article have been paid by Boehringer Ingelheim.

Objective To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary Sjogren's Syndrome (pSS). Methods Pubmed was searched between February 1996 and December 2018 using a combination of MESH terms related to pSS and ILD. Selected works were subjected to blind evaluation by two authors and a senior author in case of disagreement. The work followed PRISMA guidelines and was registered on PROSPERO (CRD42018118669). Results About 20% of pSS patients have ILD, with a 5-y survival of 84% and a need for supplemental oxygen in the 11–33% range. A significant proportion of ILD patients are seronegative without sicca syndrome. ILD seems to be associated with higher levels of Lactic Dehydrogenases and positivity for Anti-Ro52k. The prevalent pattern in High Resolution Computed Tomography is Nonspecific Interstitial Pneumonia (NSIP), but all other patterns can be present. No difference in mortality was found between patients with NSIP and Usual Interstitial Pneumonia patterns. Amyloidosis and primary lung lymphoma can be observed in about 10% of pSS patients. Conclusion The recognition of pSS underlying an ILD can be challenging in seronegative patients with no or mild sicca symptoms. A complete diagnostic assessment, including minor salivary glands and, in some cases, lung biopsy, should be performed on all patients at risk. A better recognition of the clinical or serological markers of ILD progression in these patients is warranted to drive the physicians to an early diagnosis and an effective treatment.

This article discusses a selection of the scientific presentations in the field of interstitial lung diseases (ILDs) that took place at the 2019 European Respiratory Society International Congress in Madrid, Spain. There were sessions from all four groups within Assembly 12: group 12.01 “Idiopathic interstitial pneumonias”, group 12.02 “ILDs/diffuse parenchymal lung diseases (DPLDs) of known origin”, group 12.03 “Sarcoidosis and other granulomatous ILDs/DPLDs” and group 12.04 “Rare ILDs/DPLDs”. The presented studies brought cutting-edge developments on several aspects of these conditions, including pathogenesis, diagnosis and treatment. As many of the ILDs are individually rare, the sharing of experiences and new data that occur during the Congress are very important for physicians interested in ILDs and ILD patients alike., The 2019 #ERSCongress in Madrid provided novel data on interstitial lung diseases https://bit.ly/3iUKMZY

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lungs associated with progressive disability. Although general practitioners (GPs) should play an important role in the COPD management, critical issues have been documented in the primary care setting. The aim of this study was to evaluate the effectiveness of an educational program for the improvement of the COPD management in a Sicilian general practice setting. The effectiveness of the program, was evaluated by comparing 15 quality-of-care indicators developed from data extracted by 33 GPs, at baseline vs. 12 and 24 months, and compared with data from a national primary care database (HSD). Moreover, data on COPD-related and all-cause hospitalizations over time of COPD patients, was measured. Overall, 1,465 patients (3.2%) had a registered diagnosis of COPD at baseline vs. 1,395 (3.0%) and 1,388 (3.0%) over time (vs. 3.0% in HSD). COPD patients with one spirometry registered increased from 59.7% at baseline to 73.0% after 2 years (vs. 64.8% in HSD). Instead, some quality of care indicators where not modified such as proportion of COPD patients treated with ICS in monotherapy that was almost stable during the study period: 9.6% (baseline) vs. 9.9% (after 2 years), vs. 7.7% in HSD. COPD-related and all-cause hospitalizations of patients affected by COPD decreased during the two observation years (from 6.9% vs. 4.0%; from 23.0% vs. 18.9%, respectively). Our study showed that educational program involving specialists, clinical pharmacologists and GPs based on training events and clinical audit may contribute to partly improve both diagnostic and therapeutic management of COPD in primary care setting, despite this effect may vary across GPs and indicators of COPD quality of care., Chronic lung disease: Education improves disease management An education program for doctors covering chronic lung disease diagnosis and management improves elements of patient care in Italy. Gianluca Trifirò at the University of Messina, Italy, and co-workers followed a cohort of 33 family doctors and 1,465 patients with chronic obstructive pulmonary disease (COPD) in Sicilian primary care for two years, comparing quality of care for patients before and after implementing the education program. The training, led by lung specialists and clinical pharmacologists, updated doctors with the latest information on COPD diagnosis, medication and disease management, and trained them in spirometry test interpretation. The team assessed the value of the program using quality-of-care indicators and asked each doctor to re-evaluate patients’ COPD diagnosis. Their results showed improvement in some areas, including spirometry testing, alongside a reduction in hospital admissions over the two-year period.

Background Fibrosing, non-idiopathic pulmonary fibrosis (non-IPF) interstitial lung diseases (fILDs) are a heterogeneous group of diseases characterized by a different amount of inflammation and fibrosis. Therapy is currently based on corticosteroids and/or immunomodulators. However, response to these therapies is highly variable, sometimes without meaningful improvement, especially in more fibrosing forms. Pirfenidone and nintedanib have recently demonstrated to reduce functional decline in patients with IPF. However, their antifibrotic mechanism makes these two drugs an interesting approach for treatment of fibrosing ILDs other than IPF. Objectives We here report our experience with antifibrotic drugs in fibrosing non-IPF ILDs patients having a progressive phenotype during immunosuppressive therapy. Methods Patients with a multidisciplinary team diagnosis of fibrosing non-IPF ILDs experiencing a progressive phenotype during treatment with corticosteroids and/or immunomodulators between October-2014 and January-2018 at our tertiary referral Center for ILDs were retrospectively analyzed. Antifibrotic therapy was administered after application with the respective health insurance company and after consent by the patient. Pulmonary-function-tests and follow-up visits were performed every 6 ± 1 months. Results Eleven patients were treated with antifibrotic drugs (8 males, mean age 62 ± 12.8 years, mean FVC% 62.8 ± 22.3, mean DLCO% 35.5 ± 10.7, median follow-up under antifibrotic treatment 11.1 months). Patients had a diagnosis of unclassifiable ILD in 6 cases, pleuroparenchymal fibroelastosis in 2 cases, idiopathic-NSIP in 1 case, asbestos-related ILD in 1 case and Hermansky-Pudlak syndrome in 1 case. Treatment before antifibrotics consisted of corticosteroids in all patients: 5 combined with Azathioprin, 1 with either methotrexate or cyclophosphamide (i.v.). Ten patients were treated with pirfenidone (2403 mg/die) and 1 with nintedanib (300 mg/die). Median FVC was 56, 56, 50%, at time points − 24, − 12, − 6 before initiation, 44% at time of initiation and 46.5% at 6 months after initiation of antifibrotic treatment. Antifibrotic treatment was generally well tolerated with a need of dose reduction in 2 cases (rash and nausea) and early termination in 3 cases. Conclusions Antifibrotic treatment may be a valuable treatment option in patients with progressive fibrosing non-IPF ILD if currently no other treatment options exist. However, prospective, randomized clinical trials are urgently needed to assess the real impact of antifibrotic therapy in these patients.

Background: Unclassifiable interstitial lung disease (uILD) is classified within the idiopathic ILDs and is regarded as an ILD where multidisciplinary review can not secure a specific diagnosis with a diagnostic confidence > 50%. While some prognostic determinants have been defined recently, radiological findings have been poorly studied and their role as predictors of survival is less clear. We aimed to assess the prognostic impact of radiological findings in uILD patients. Methods: The databases of two tertiary referral centers for ILD were reviewed for uILD. Clinical and functional data, and high resolution computed tomography (HRCT) scan images were retrospectively analyzed in 208 uILD patients. Results: Mean age was 65.6 years, 54.3% male, mean FVC 72.2%, mean DLCO 47.8%, mean ILD-GAP index 3.29, median follow-up period was 14.2 months. 75.1% showed reticulations, 80% traction bronchiectasis (TB) and 16.9% honeycombing (HC) on HRCT. Presence of TB and HC (hazards ratio [HR] 4.56, p=0.04 and 5.61, p Conclusion: Honeycombing is an independent predictor of mortality in uILD. Its inclusion in a prognostic model improves the estimation of survival in uILD patients.

Background: The term “Interstitial Pneumonia with Autoimmune Features (IPAF)” is used to describe patients with Interstitial Lung Disease in combination to clinical, serological and/or pulmonary features that are suggestive, but insufficient to satisfy classification criteria of a specific Connective Tissue Disease (CTD). Some retrospective studies available in literature described patient cohorts with IPAF heterogenous in terms of clinical, serological, and radiographic manifestations Objectives: To prospectively recruit a cohort of consecutive ILD patients classified as IPAF or as affected by Idiopathic Pulmonary Fibrosis (IPF); to describe their clinical, serological, and radiological features by a multi-disciplinar team composed by Pulmonologists, Radiologists, and Rheumatologists, comparing IPAF and IPF patients. Methods: In the lasts 2 years, they were enrolled 45 patients with IPAF and 143 with IPF among a total of 506 patients with Interstitial Lung Disease (ILD). All patients were evaluated clinically by both rheumatologists and pulmonologists, also by means of chest high resolution computed tomography (hrCT), pulmonary function tests (PFT), and nailfold videocapillaroscopy. Results: In IPAF cohort the most common characteristics from the clinical, serological and morphological domain were Raynaud’s phenomenon (RP) (31.1%) antinuclear antibodies positivity with titre ≥1/320 or any titre for centromeric or nucleolar pattern (17.7%) and nonspecific interstitial pneumonia (68.8%) respectively. The majority of patient (88.9%) had the minimum of 2 criteria at the recruitment. Female gender was more common in IPAF compared to IPF (62.2% vs 23%, p Conclusion: IPAF criteria recruit a rare cohort of patients with a disease probably less severe than IPF, even though clinically relevant. Further prospective studies may better define the long-term prognosis of ILD in IPAF. The follow-up of these patients by a multi-disciplinary team may be useful in order to early recognize and treat the new cases of CTDs. Some IPAF criteria probably are useless due to their high specificity for definite CTD and the classification need a revision in the light of the prospective experiences. Nevertheless, IPAF classification can recruit incomplete form or early onset of CTD that can allow a timely treatment in patients without a structured damage. References: [1] Sambataro G, Sambataro D, Torrisi SE, Vancheri A, Pavone M, Rosso R, Schisano M, Crimi C, Pignataro F, Fischer A, Del Papa N, Vancheri C. State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances. Eur Respir Rev2018:27(148) Disclosure of Interests: None declared

Background Interstitial lung disease (ILD) is the most frequent pulmonary impairment in Sjogren’s syndrome (SS). The diagnosis is challenging, as there are not specific tests (i.e. autoantibodies or pulmonary function tests) or symptoms. Chest CT is the gold standard. Semiquantitative visual scores (SQCT) estimate ILD extent, though burdened by relevant intra-, inter-rater variability. Quantitative chest CT (QCT) is a promising method to assess ILD severity Objectives: to verify if QCT assessment could identify SS subjects affected by ILD and to identify those SS patients with an extensive lung disease. Methods: in this multi-center, cross-sectional, and retrospective study, subjects affected by SS and with a chest CT were enrolled. A blind and centralized SQCT assessment was carried out in order to calculate both Goh and Taouli scores. An operator-independent analysis of all CTs with an open-source software (i.e. Horos), provided the QCT indexes. Patients were clustered in cohorts according to ILD extent. Differences in QCT indexes distribution were analyzed using non-parametric tests. Results 102 consecutive SS patients were enrolled. ILD prevalence was 36% (36/102). There was a difference in QCT indexes’ distribution in SS-ILD versus SS without ILD (p 20% (according to Goh score) had QCT indexes statistically different from those with a limited ILD extension (p 0.7; the best QTC index was: tSkew AUC 0.87 (95CI 0.78-0.95), p Conclusion QCT indexes are a serious alternative to visual scorings in ILD related to autoimmune diseases. This innovative tool will open up a potential research area in SS as it appears able to select ILD patients with an extensive lung impairment and likewise a worse prognosis. We are confident that in the next future, QCT will have a pivotal role in the diagnosis, monitoring and treatment pathway of ILD associated to SS. References [1] Silva M, Milanese G, Seletti V, Ariani A, Sverzellati N. Pulmonary quantitative CT imaging in focal and diffuse disease: current research and clinical applications. Br J Radiol2018; 91: 20170644. Disclosure of Interests None declared

Introduction: Connective Tissue Diseases (CTDs) are systemic autoimmune conditions characterized by frequent lung involvement. This usually takes the form of Interstitial Lung Disease (ILD), but Obstructive Lung Disease (OLD) and Pulmonary Artery Hypertension (PAH) can also occur. Lung involvement is often severe, representing the first cause of death in CTD. The aim of this study is to highlight the role of Pulmonary Function Tests (PFTs) in the diagnosis and follow up of CTD patients. Main body: Rheumatoid Arthritis (RA) showed mainly an ILD with a Usual Interstitial Pneumonia (UIP) pattern in High-Resolution Chest Tomography (HRCT). PFTs are able to highlight a RA-ILD before its clinical onset and to drive follow up of patients with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO). In the course of Scleroderma Spectrum Disorders (SSDs) and Idiopathic Inflammatory Myopathies (IIMs), DLCO appears to be more sensitive than FVC in highlighting an ILD, but it can be compromised by the presence of PAH. A restrictive respiratory pattern can be present in IIMs and Systemic Lupus Erythematosus due to the inflammatory involvement of respiratory muscles, the presence of fatigue or diaphragm distress. Conclusions: The lung should be carefully studied during CTDs. PFTs can represent an important prognostic tool for diagnosis and follow up of RA-ILD, but, on their own, lack sufficient specificity or sensitivity to describe lung involvement in SSDs and IIMs. Several composite indexes potentially able to describe the evolution of lung damage and response to treatment in SSDs are under investigation. Considering the potential severity of these conditions, an HRCT jointly with PFTs should be performed in all new diagnoses of SSDs and IIMs. Moreover, follow up PFTs should be interpreted in the light of the risk factor for respiratory disease related to each disease.

Background: The gender–age–physiology (GAP) model was developed to predict the risk of death. Comorbidities are common in idiopathic pulmonary fibrosis (IPF) and may impact on survival. We evaluated the ability of comorbidities to improve prediction of survival in IPF patients beyond the variables included in the GAP model. Methods: We developed a prediction model named TORVAN using data from two independent cohorts. Continuous and point-score prediction models were developed with estimation of full and sparse versions of both. Model discrimination was assessed using the C-index and calibrated by comparing predicted and observed cumulative mortality at 1–5 years. Results: Discrimination was similar for the sparse continuous model in the derivation and validation cohorts (C-index 71.0 versus 70.0, respectively), and significantly improved the performance of the GAP model in the validation cohort (increase in C-index of 3.8, p=0.001). In contrast, the sparse point-score model did not perform as well in the validation cohort (C-index 72.5 in the derivation cohort versus 68.1 in the validation cohort), but still significantly improved upon the performance of the GAP model (C-index increased by 2.5, p=0.037). Conclusions: The inclusion of comorbidities in TORVAN models significantly improved the discriminative performance in prediction of risk of death compared to GAP.

Background: Interstitial lung disease (ILD) is a frequent manifestation of Sjögren's syndrome (SS), an autoimmune disease of salivary and lacrimal glands, and affects approximately 20% of patients. No clinical or serological features appear to be useful to predict its presence, severity or progression, and chest high-resolution computed tomography (CT) remains the gold standard for diagnosis. Semiquantitative CT (SQCT) based on visual assessment (Goh and Taouli scoring) can estimate ILD extent, although it is burdened by relevant intra- and interobserver variability. Quantitative chest CT (QCT) is a promising alternative modality to assess ILD severity. Aim: To determine whether QCT assessment can identify extensive or limited lung disease in patients with SS and ILD. Methods: This multi-center, cross-sectional and retrospective study enrolled patients with SS and a chest CT scan. SQCT assessment was carried out in a blinded and centralized manner to calculate both Goh and Taouli scores. An operator-independent analysis of all CT scans with the open-source software platform Horos was used to evaluate the QCT indices. Patients were classified according to the extent of ILD and differences in QCT index distribution were investigated with non-parametric tests. Results: From a total of 102 consecutive patients with SS, the prevalence of ILD was 35.3% (36/102). There was a statistically significant difference in QCT index distribution between the SS with ILD and SS without ILD groups (p20% (by Goh score) had a QCT index statistically different from those with limited ILD extent (p

Several imaging findings of thoracic diseases have been referred—on chest radiographs or CT scans—to signs, symbols, or naturalistic images. Most of these imaging findings include the air bronchogram sign, the air crescent sign, the arcade-like sign, the atoll sign, the cheerios sign, the crazy paving appearance, the comet-tail sign, the darkus bronchus sign, the doughnut sign, the pattern of eggshell calcifications, the feeding vessel sign, the finger-in-gloove sign, the galaxy sign, the ginkgo leaf sign, the Golden-S sign, the halo sign, the headcheese sign, the honeycombing appearance, the interface sign, the knuckle sign, the monod sign, the mosaic attenuation, the Oreo-cookie sign, the polo-mint sign, the presence of popcorn calcifications, the positive bronchus sign, the railway track appearance, the scimitar sign, the signet ring sign, the snowstorm sign, the sunburst sign, the tree-in-bud distribution, and the tram truck line appearance. These associations are very helpful for radiologists and non-radiologists and increase learning and assimilation of concepts.Therefore, the aim of this pictorial review is to highlight the main thoracic imaging findings that may be associated with signs, symbols, or naturalistic images: an “iconographic” glossary of terms used for thoracic imaging is reproduced—placing side by side radiological features and naturalistic figures, symbols, and schematic drawings.

Background:Nailfold Videocapillaroscopy (NVC) is an essential tool for the assessment of Raynaud’s Phenomenon (RP) among the Scleroderma Spectrum Disorders (SSDs). Recently, NVC abnormalities have been associated with a diagnosis of Idiopathic Inflammatory Myopathies (IIMs), independently of the presence of RP (1). Moreover, both SSDs and IIMs are commonly associated with Interstitial Lung Disease (ILD), which is the main cause of mortality in these conditions.Objectives:To verify whether NVC may allow a better diagnostic classification in a cohort of patients with ILD followed by pulmonologists.Methods:361 patients affected by ILD were prospectively enrolled in a 30-months observational study. All these patients were clinically evaluated by rheumatologists and pulmonologists together and performed general blood tests, autoantibody research, chest High-Resolution Computed Tomography and NVC. The latter was considered positive in the presence of avascular areas or giant capillaries, and also the presence of Bushy Capillaries (BCs) was recorded.Results:NVC was positive in 17.7% of ILD patients, and a third of these patients did not present RP. Patients with NVC abnormalities had a diagnosis of definite Connective Tissue Disease in 78.1% of cases. NVC resulted decisive in 25% of patients with a final diagnosis of Systemic Sclerosis according to the ACR/EULAR 2013 criteria. The presence of BCs and/or NVC+ in ILD patients with normal serum levels of muscular enzymes was associated with amyopathic IIM (BCs= OR 3.9, 95CI 1.05-14.38, p=0.04; NVC+= OR 5, 95CI 1.29-19.3 p=0.02; BCs and/or NVC+= OR 5.41 95CI 1.24-23.48 p=0.02), regardless the presence of RP.Conclusion:NVC proved to be a valid tool in the correct assessment of ILD patients secondary to SSDs and amyopathic IIMs. Therefore, it could be considered in the diagnostic evaluation of patients affected by ILD, regardless of the presence of RP.References:[1]Sebastiani M et al. Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and possible clinical associations: results of a multicenter International Study.J Rheumatol2019; 46: 279-284Table 1.Comparison between ILD patients with and without NVC positivity..ItemsNVC+ patientsNVC- patientspNumber64297Mean Age (±SD)61.4±13.367.8±9.80.001Female%65.649.10.01RP%68.717.1HRCT patterns%NSIP51.536.80.02OP3.18n.s.UIP-like31.1544.8n.s.DIP1.53.4n.s.LIP1.50.4n.s.Indeterminate10.96.7n.s.Final Diagnosis%SSDs45.31IIMs256.4Other CTDs6.213.5n.s.IPAF10.919.5n.s.IPF7.827.90.0007Legend:DIP: Desquamative Interstitial Pneumonia; HRCT: High Resolution Computed Tomography; IIMs: Idiopathic Inflammatory Myopathies, Poly/dermatomyositis, antisynthetase syndrome; IPAF: Interstitial Pneumonia with Autoimmune Features; IPF: Idiopathic Pulmonary Fibrosis; LIP: Lymphocytic Interstitial Pneumonia; NSIP: Nonspecific Interstitial Pneumonia; OP: Organising Pneumonia; RP: Raynaud’s Phenomenon; SSDs: Scleroderma Spectrum Disorders, Systemic Sclerosis + Mixed Connective Tissue Disease; UIP: Usual Interstitial Pneumonia.Disclosure of Interests:Gianluca Sambataro: None declared, Domenico Sambataro: None declared, Francesca Pignataro: None declared, Nicoletta Del Papa: None declared, Michele Colaci: None declared, Lorenzo Malatino: None declared, Alessandro Libra: None declared, Fabio Pino: None declared, Sebastiano Emanuele Torrisi Speakers bureau: Boehringer Ingelheim; F. Hoffmann-La Roche Ltd., Stefano Palmucci Consultant of: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Delphi International Srl, and F. Hoffmann-La Roche Ltd., Lorenzo Cavagna: None declared, Carlo Vanchieri Grant/research support from: F. Hoffmann-La Roche Ltd., Consultant of: AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini, Speakers bureau: AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini

Idiopathic pulmonary fibrosis (IPF) is a chronic and devastating disease of unknown etiology, characterized by irreversible morphological changes, ultimately leading to lung fibrosis and death. In recent years, significant progress has been achieved in understanding the pathogenesis of IPF. Moreover, we assisted to the conceptual change of the pathogenic hypothesis that currently considers IPF as a primarily fibrotic driven disease. However, despite the undeniable progress, the diagnosis of IPF remains still very complex requiring the presence of a team of experts to achieve the highest level of diagnostic confidence. The advent of antifibrotics has radically changed the treatment landscape of IPF and new promising drugs are currently under evaluation. Furthermore, a more extensive use of non-pharmacological treatments has also to be encouraged in all patients both to reduce symptoms and improve quality of life.

Background The term Interstitial Pneumonia with Autoimmune Features (IPAF) describes patients with Interstitial Lung Diseases (ILDs) and clinical or serological features of autoimmune diseases insufficient to reach a specific classification of a Connective Tissue Disease (CTD). Currently, retrospective studies on IPAF patients have proven to be heterogeneous in general characteristics, outcomes and High-Resolution Computed Tomography (HRCT) pattern. This study aims to describe for the first time the clinical, serological and radiological features of a prospective cohort of IPAF patients. This cohort is then compared to a group of patients with Idiopathic Pulmonary Fibrosis (IPF). Material and methods From 626 consecutive ILD patients evaluated, 45 IPAF and a comparison cohort of 143 IPF patients were enrolled. All patients underwent clinical assessment with rheumatologic and respiratory evaluation, HRCT, Pulmonary Function Tests and Nailfold Videocapillaroscopy. Results The IPAF patients had a predominance of female gender (62.12%) with a median age of 66 years. The most common findings were: Nonspecific Interstitial Pneumonia (NSIP, 68.89%), Antinuclear Antibody positivity (17.77%) and Raynaud Phenomenon (31.11%). In comparison with IPF, IPAF patients showed younger age, better performances in Pulmonary Function Tests, less necessity of O2 support and predominance of female sex and NSIP pattern. Discussion This is the first report of a prospective cohort of IPAF patients. IPAF patients seem to have a less severe lung disease than IPF. IPAF criteria probably need to be revisited and validated, but their capacity to recruit patients with incomplete forms or early onset of CTD could be useful for further research.

Background: correlation between pulmonary function tests (PFTs) and CT-histogram derived indexes is poorly known in Idiopathic Pulmonary Fibrosis (IPF). Objective: To investigate correlation between PFTs (FVC and DLCO) and CT-histogram derived indexes in a cohort of patients (pts) with IPF. Methods: 42 IPF pts having at least two HRCT (baseline and follow-up) and two PFTs available collected no more than 1 month from HRCT evaluation were analyzed. The extent of fibrotic disease was quantified on HRCT examinations calculating Kurtosis, High Attenuation Area (HAA) and Fibrotic Area (FA) indexes. Pearson’s correlation coefficient was performed to assess the strength of association between pulmonary function tests and HRCT indexes. Results: Considering baseline HRCT and PFTs, Pearson correlation analysis revealed moderate correlations between Kurtosis and FVC (r=0.58 with p=0.0001), Kurtosis and DLCO (r=0.52 with p=0.0005), HAA and FVC (r=-0.56 with p=0.0001), HAA and DLCO (r=-0.48 with p=0.0017), FA and FVC (r=-0.56 with p=0.0002), and FA and DLCO (r=-0.49 with p=0.0013). On follow-up, analyzing HRCT and PFTs, Kurtosis and FVC showed a positive strong correlation (r=0.62 with p Conclusions: HRCT quantification indexes showed a moderate or good strength of association with pulmonary function tests; therefore, they may be useful for radiologists in the monitoring of IPF disease.

Introduction: The term Interstitial Pneumonia with Autoimmune Features (IPAF) has been proposed to classify patients with Interstitial Lung Disease (ILD) associated with autoimmune signs not classifiable for a specific Connective Tissue Disease (CTD). Currently, no prospective IPAF cohort are reported. Aims and Objectives: To describe a prospective cohort of IPAF patients. Methods: The study was conducted according to the declaration of Helsinki. A total of 170 consecutive ILD patients with at least one IPAF criteria were considered in the last year (Fischer A, Eur Respir J 2015; 46 (4): 976-987). From these, 58 patients were able to satisfy classification criteria for CTDs, while 33 patients were classified as IPAF. Results: IPAF patients (69.7% females) referred a history of smoke in 51.5% of cases and reported a restrictive pattern in Pulmonary Function Tests in 66.7% of cases. A clinical domain was present in 72.7% of patients, whereas serological and morphological domains respectively in 72.7% and 87.9% of cases. The most frequent item from each domain were arthritis (42.4%), Antinuclear Antibodies (ANA) (30.3%) and Nonspecific Interstitial Pneumonia (75.8%) as HRCT pattern. No cases of ulcers, telangiectasia and mechanic’s hand were reported. Only ANA, Rheumatoid Factor, anti-SSA, anti DsDNA and Anti Citrullinated Protein Antibodies were found as serological domain. Conclusions: This study suggests that most of IPAF patients have a clinically relevant ILD without serological and clinical items highly specific for CTDs. When these items were present, patients were generally able to satisfy specific CTD criteria. Probably, some of IPAF patients can have an early form of CTDs.

Background: the predictive role of CT-histogram indexes in assessing survival was poorly studied in IPF. Objective: To investigate the accuracy of CT-histogram derived indexes in the assessment of survival in IPF patients (pts). Methods: 42 IPF pts with a follow-up time of 3 years were retrospectively collected; HRCT and pulmonary function tests (FVC and DLCO) performed at diagnosis were analyzed; the extension of fibrosis was quantified on HRCT using Kurtosis, Skewness, Mean Lung Density (MLD), High Attenuation Areas (HAA%) and Fibrotic Areas (FA%). Univariate Cox-regression analysis assessed Hazard ratios for each variable. A Multivariate model including Skewness, FVC, DLCO and age tested their prognostic value in assessing survival. Through ROC analysis, threshold values demonstrating the best sensitivity and specificity in predicting mortality were identified and used as cut-off points to graph Kaplan-Meier curves specific for the CT-indexes. Results: Kurtosis, Skewness, MLD, HAA% and FA% were good predictors of mortality (HR 0.44, 0.74, 1.01, 1.12, 1.06; p=0.03, p=0.01, p=0.02, p=0.02 and p=0.017 respectively). Skewness, which demonstrated the lowest AIC value (55.52), was considered the best analyzed CT-index in predicting mortality. Significant survival differences considering proposed cut-off points were also demonstrated according to Kurtosis (p=0.02), Skewness (p=0.005), MLD (p=0.003), HAA% (p=0.009) and FA% (p=0.02) – obtained from quantitative HRCT analysis at the diagnosis time. Conclusions: CT-histogram derived indexes may provide an accurate estimation of survival in a population of IPF patients since the time of diagnosis.

Interstitial lung diseases (ILDs) are a large and heterogeneous group of lung disorders characterized by primary involvement of the lung interstitium. Several studies point out their increasing incidence and global burden leading to a growing interest and massive literature production in the last few years.

The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful.

Idiopathic Pulmonary Fibrosis (IPF) is a severe parenchymal lung disease characterized by an intense deposition of collagen in the interstitial spaces. The introduction of anti-fibrotic drugs increased patients' life expectancy highlighting the role of comorbidities in patients' management and prognosis. IPF is frequently associated with other diseases mainly because of its onset during middle age and sometimes because of the presence of common pathogenic pathways such as in the case of lung cancer. Comorbidities may differently influence prognosis of IPF patients. However, except for major impacting ones as LC, PH and cardiovascular diseases, data exploring their impact on prognosis are still few and sometimes conflicting highlighting the need of new large and targeted studies. In this review we discuss the current knowledge on the most common comorbidities associated with IPF (cardiovascular diseases, pulmonary hypertension, lung cancer, emphysema, gastro-oesophageal reflux and depression), focusing on their prognostic role.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I–III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause, occurring in adults, limited to the lungs and associated with the pathologic and radiologic pattern of usual interstitial pneumonia. Prognosis is poor, and most patients die of respiratory failure within 3 to 6 years from the onset of symptoms. Although our understanding of the pathogenesis of IPF has improved over the past two decades, the mechanisms responsible for this disorder have not been clearly defined. Aging is the single most important risk factor, but genetic, environmental, and diverse exogenous factors such as smoking, viral infections, chronic tissue injury (i.e., gastroesophageal reflux disease, traction injury) play contributory roles. In this review, we focus on pathogenetic mechanisms that we think are crucial for the initiation of the fibrotic process and for its progressive evolution. In the early stage of the disease, in the context of the permissive genetic background combined with the presence of specific risk factors, alveolar epithelial cells play a leading role. Subsequent evolution of the fibrotic process and its lethal progression is likely due to the abnormal tissue repair process that takes place in the lung and to the inability to counteract this process. In this phase of the disease, fibroblasts assume a crucial role. Current pharmacological treatment strategies for IPF have only modest value, principally by slowing the course of disease progression. Unfortunately, improvement or cure has not yet been achieved with pharmacological agents. The challenge for the future is to improve the comprehension of the mechanisms involved in the inception and evolution of IPF and their articulated interactions. This is fundamental not only to conceive and develop new drugs against this dreadful disease but also to apply different therapeutic approaches such as drug repositioning and personalized therapies in the management of IPF.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive parenchymal lung disease characterized by a median survival of 3–5 years following diagnosis. The diagnosis is based on clinical, radiological and histopathological evaluation. Therefore, a multidisciplinary team is needed to reach the correct diagnosis. For a long time, supportive care and lung transplantation in selected cases, have been considered the only possible treatments for IPF. In the last decade many studies have investigated IPF pathogenesis, leading to an improved knowledge of the mechanisms underlying the disease and to the approval of two new drugs for IPF treatment (pirfenidone and nintedanib). The therapeutic approach of IPF cannot be limited to the administration of antifibrotic drugs, but it is necessary for improving the quality of life of patients and for facilitating, as far as possible, the performance of normal daily activities and relationships. IPF patients are also afflicted by disease-related complications such as gastroesophageal reflux, pulmonary hypertension, acute exacerbations and an increased risk of developing lung cancer. The clinician who treats IPF patients, should also treat these possible complications to slow disease progression, thus maintaining the possibility of a pulmonary transplantation.

The aim of this manuscript is to describe radiological findings of extra-pulmonary sarcoidosis. Sarcoidosis is an immune-mediated systemic disease of unknown origin, characterized by non-caseating epitheliod granulomas. Ninety percent of patients show granulomas located in the lungs or in the related lymph nodes. However, lesions can affect any organ. Typical imaging features of liver and spleen sarcoidosis include visceromegaly, with multiple nodules hypodense on CT images and hypointense on T2-weighted MRI acquisitions. Main clinical and radiological manifestations of renal sarcoidosis are nephrolithiasis, nephrocalcinosis, and acute interstitial nephritis. Brain sarcoidosis shows multiple or solitary parenchymal nodules on MRI that enhance with a ring-like appearance after gadolinium. In spinal cord localization, MRI demonstrates enlargement and hyperintensity of spinal cord, with hypointense lesions on T2-weighted images. Skeletal involvement is mostly located in small bone, showing many lytic lesions; less frequently, bone lesions have a sclerotic appearance. Ocular involvement includes uveitis, conjunctivitis, optical nerve disease, chorioretinis. Erythema nodosum and lupus pernio represent the most common cutaneous manifestations encountered. Sarcoidosis in various organs can be very insidious for radiologists, showing different imaging features, often non-specific. Awareness of these imaging features helps radiologists to obtain the correct diagnosis. • Systemic sarcoidosis can exhibit abdominal, neural, skeletal, ocular, and cutaneous manifestations. • T2 signal intensity of hepatosplenic nodules may reflect the disease activity. • Heerfordt’s syndrome includes facial nerve palsy, fever, parotid swelling, and uveitis. • In the vertebrae, osteolytic and/or diffuse sclerotic lesions can be found. • Erythema nodosum and lupus pernio represent the most common cutaneous manifestations.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia characterized by a poor survival, even worse than many cancers. Recent studies have demonstrated that IPF and cancer share several cellular and molecular alterations related to epigenetic and genetic changes, altered regulation of apoptosis, abnormal response to regulatory signals, abnormal expression of microRNAs (mRNAs), reduced cell-to-cell communication and activation of specific signaling pathways. This leads to the hypothesis that IPF can be considered, in some respects, a cancer-like disease. This correlation may help in understanding the pathogenesis of IPF by exploiting the great knowledge of the biological mechanisms studied in cancer but it may also help in increasing the awareness of this disease at public, political and even at healthcare level. In addition, the identification of common pathogenic pathways between the two diseases may stimulate new clinical trials with cancer drugs, as in the case of nintedanib, and drugs combinations or different lines of drugs as largely experimented in cancer. Keywords: interstitial lung diseases, idiopathic pulmonary fibrosis, cancer, epigenetic alterations, cell to cell communications, signal transduction pathways, myofibroblasts, TGF-β, tyrosine kinases

Objectives To illustrate the clinical and radiological features of idiopathic interstitial pneumonias (IIPs), according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) classification updated in 2013. Methods IIPs include a subset of diffuse and restrictive lung diseases, resulting from damage to the parenchyma characterised by inflammation and fibrosis of the interstitium. Classification into major and rare IIPs is based on the 2013 ATS/ERS committee. Results The diagnosis of idiopathic pulmonary fibrosis (IPF) needs to exclude other well-known causes of interstitial lung diseases. According to the 2011 evidence-based guidelines, usual interstitial pneumonia (UIP) can be diagnosed by HRCT when all criteria are fulfilled. Non-specific interstitial pneumonia (NSIP) is characterised by patchy ground-glass opacities and irregular linear/reticular opacities. The imaging patterns of respiratory bronchiolitis associated-interstitial lung disease (RB-ILD) and desquamative interstitial pneumonia (DIP) show centrolobular nodules and ground-glass opacities. Cryptogenic organising pneumonia (COP) consists of patchy peripheral or peribronchial consolidations, while ground-glass opacities are typically associated with diffuse lung consolidation, evolving to fibrosis, in acute interstitial pneumonia (AIP). Rare IIPs include lymphoid interstitial pneumonia and idiopathic pleuro-parenchymal fibroelastosis (IPPFE). Conclusions The knowledge of IIP imaging features on HRCT images help radiologists in diagnosis. Moreover, the overlap of imaging features needs a multidisciplinary approach. Teaching Points • UIP findings are reticulations, bronchiectasis, honeycombing and absence of inconsistent features. • Bilateral patchy ground-glass areas represent the most encountered features in NSIP. • Poorly defined centrilobular nodules are typical of RB-ILD, whereas a ground-glass appearance is typical of DIP. • HRCT features of COP include characteristic peripheral or peribronchial patchy consolidations. • Rare IIPs include idiopathic LIP and idiopathic pleuro-parenchymal fibroelastosis (PPFE).