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Introduction Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. Methods Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. Results 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6 min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO Conclusions Patients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Introduction: Idiopathic pulmonary fibrosis (IPF) prognosis is heterogeneous despite antifibrotic treatment. Cluster analysis has proven to be a useful tool in identifying interstitial lung disease phenotypes, which has yet to be performed in IPF. The aim of this study is to identify phenotypes of IPF with different prognoses and requirements. Methods: Observational retrospective study including 136 IPF patients receiving antifibrotic treatment between 2012 - 2018. Six patients were excluded due to follow-up in other centers. Cluster analysis of 30 variables was performed using approximate singular value-based tensor decomposition method and comparative statistical analysis. Results: The cluster analysis identified 3 different groups of patients according to disease behavior and clinical features, including mortality, lung transplant and progression-free survival time after 3-year follow-up. Cluster 1 (n=60) was significantly associated (p=0.02) with higher mortality. Diagnostic delay was the most relevant characteristic of this cluster, as 48% of patients had ≥ 2 years from first respiratory symptoms to antifibrotic treatment initiation. Cluster 2 (n=22) had the longest progression-free survival time and was correlated to subclinical patients evaluated in the context of incidental findings or familial screening. Cluster 3 (n=48) showed the highest percentage of disease progression without cluster 1 mortality, with metabolic syndrome and cardiovascular comorbidities as the main characteristics. Conclusion: This cluster analysis of IPF patients suggests that diagnostic and treatment delay are the most significant factors associated with mortality, while IPF progression was more related to metabolic syndrome and cardiovascular comorbidities.

Introduction Idiopathic pulmonary fibrosis (IPF) prognosis is heterogeneous despite antifibrotic treatment. Cluster analysis has proven to be a useful tool in identifying interstitial lung disease phenotypes, which has yet to be performed in IPF. The aim of this study is to identify phenotypes of IPF with different prognoses and requirements. Methods Observational retrospective study including 136 IPF patients receiving antifibrotic treatment between 2012 and 2018. Six patients were excluded due to follow-up in other centres. Cluster analysis of 30 variables was performed using approximate singular value-based tensor decomposition method and comparative statistical analysis. Results The cluster analysis identified three different groups of patients according to disease behaviour and clinical features, including mortality, lung transplant and progression-free survival time after 3-year follow-up. Cluster 1 (n=60) was significantly associated (p=0.02) with higher mortality. Diagnostic delay was the most relevant characteristic of this cluster, as 48% of patients had ≥2 years from first respiratory symptoms to antifibrotic treatment initiation. Cluster 2 (n=22) had the longest progression-free survival time and was correlated to subclinical patients evaluated in the context of incidental findings or familial screening. Cluster 3 (n=48) showed the highest percentage of disease progression without cluster 1 mortality, with metabolic syndrome and cardiovascular comorbidities as the main characteristics. Conclusion This cluster analysis of IPF patients suggests that diagnostic and treatment delay are the most significant factors associated with mortality, while IPF progression was more related to metabolic syndrome and cardiovascular comorbidities., Diagnostic delay and cardiovascular comorbidities impact IPF outcomes https://bit.ly/3lk2Z5y

Background and objective The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. Methods This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. Results In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. Conclusion In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

BackgroundNon-invasive biomarkers for the assessment of disease severity in idiopathic pulmonary fibrosis (IPF) are urgently needed. Calprotectin belongs to the S-100 proteins produced by neutrophils, which likely contribute to IPF pathogenesis. Calprotectin is a well-established biomarker in inflammatory bowel diseases. In this cross-sectional study, we aimed to establish the potential role of calprotectin as a biomarker in IPF. Specifically, we hypothesised that patients with IPF have higher serum calprotectin levels compared with healthy controls, and that calprotectin levels are associated with disease severity.MethodsBlood samples were obtained from healthy volunteers (n=26) and from two independent IPF cohorts (derivation cohort n=26, validation cohort n=66). Serum calprotectin levels were measured with a commercial kit adapted for that purpose and compared between healthy controls and patients with IPF. Clinical parameters, including forced vital capacity, diffusing capacity for carbon monoxide (DLCO) and the Composite Physiologic Index (CPI), were correlated with calprotectin serum levels.ResultsThe IPF derivation cohort showed increased serum calprotectin levels compared with healthy controls (2.47±1.67 vs 0.97±0.53 µg/mL, pConclusionSerum calprotectin levels are significantly increased in patients with IPF compared with healthy controls and correlate with DLCO and CPI. Calprotectin might be a potential new biomarker for disease severity in IPF.

Telomere dysfunction has been related to post-transplant morbi-mortality.Study aim´s: post-transplant survival and morbidity evaluation in fibrotic ILD with and without telomeropathy Methods: Prospective observational study of fibrotic ILD cases from Bellvitge Hospital that underwent lung transplant(LT) in V.Hebron Hospital. Telomere length was measured from lymphocytes DNA, through quantitative PCR. Whole-exome sequencing for telomere maintenance genes was performed in case of telomere shortening(TS) Results: 20 patients(IPF 40%, FPF 40%, hypersensitivity pneumonitis 5%, CPFE 5%, descamative interstitial pneumonia 5%, CTD-ILD 5%). Twelve(60%) patients had TS and mutations in RTEL1, TERT, DKC1,PARN. A similar pre-LT functional status was reported regardless of TS. LT morbidity: patients with TS had a greater need for extracorporeal circulation, longer ICU admission period and higher number of hospital admissions(p=0.033) with 2.9 times higher risk for readmission[(CI 1.11-7.59)(p=0.029)]; being the only ones with hematological complications during the first month. At long term, no differences in morbidity were found regardless of TS. Survival: 17/20(85%) patients,[10/12(83.3%) with TS and 7/8(87.5%) without]. Quality of life: overall mean FVC post-LT increase of 0.55 liters(p=0.0003)[CI95%: 0.21;0.89]. Oxygen withdrawal in 16/17(94.1%) cases with independence for daily life activities[15/17(88.2%)] and active life[11/17(64.7%)] regardless of TS(p=1.000) Conclusions: Post-LT morbidity differs accoding to elapsed time from LT and genetic susceptibility.However, a positive impact in post-LT survival and quality of life was shown for fibrotic ILD regardless of telomeropathy

© 2021 The Authors., Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients., R.P laboratory was funded by grants P17-01401 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain supported by FEDER funds), CIBER 576/805_ER16PE06P2016 and MINECO from the Spanish Government (INNPACTO, IPT-2012-0674-090000). M.M-M. laboratory was funded by Instituto de Salud Carlos III PI18/00367, supported by FEDER (Fondos Europeos de Desarrollo Regional (a way to build Europe)), JC received funds from MINECO CICYT SAF2014-55322-P, and GG laboratory was funded by grant SAF2015-68073-R (MINECO/FEDER) supported by FEDER funds. C.MG and R G-L are granted by the CIBERER.

BACKGROUND AND OBJECTIVE The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications. METHODS Consecutive Spanish patients were included at diagnosis and followed up for 3 years. DNA blood samples from a Mexican cohort were used to validate the results found in Spanish sporadic IPF. Prior to treatment, telomere length was measured through quantitative polymerase chain reaction (qPCR) and Southern blot. Outcome was assessed according to mortality or need for lung transplantation. A multivariate regression logistic model was used for statistical analysis. RESULTS Family aggregation, age of

Introduction and Aim: Pirfenidone and nintedanib are anti-fibrotic approved treatments for idiopathic pulmonary fibrosis (IPF). Its efficacy and safety in other fibrotic interstitial lung diseases (ILD) is under study in clinical trials. The aim was to analyse the effect of these drugs in non-IPF progressive fibrotic patients that couldn’t be included in these trials. Methods: Multicenter retrospective study of 34 progressive PF non-IPF patients treated with anti-fibrotic drugs. Demographic, clinical data and treatment-related variables were evaluated. The reason to start off-label anti-fibrotic was disease progression with previous therapy and exclusion from clinical trials. Results: Patients with non-IPF progressive PF were: 38% unclassifiable PF (UPF), 20% familial pulmonary fibrosis (FPF), 18% CTD-ILD, 15% chronic hypersensitivity pneumonitis (CHP) and 9% pneumoconiosis. Mean age was 67±12 years, 74% were male and 47% ex-smokers. 21% of cases had usual interstitial pneumonia HRCT pattern. Mean FVC was 66%±23 and DLCO 45%±12. Co-medications were: low-dose prednisone (20), mycophenolate (5) and sirolimus (1). Twenty-four subjects (71%) received pirfenidone and ten (29%) nintedanib. After one year, a FVC decrease of 5-10% was observed in only 3 patients (1 CHP, 1 pneumoconiosis, 1 UPF), while others showed stability or improvement. Main reported adverse effects were: 20% hypertransaminasemia, 27% diarrhea and 15% weight loss, requiring 5 patients to stop therapy. Conclusion: After one year of anti-fibrotic therapy, most patients with non-IPF progressive PF showed functional stability. Clinical trials are mandatory to evaluate their potential efficacy, but these drugs are a safe option in progressive PF patients.

[Background]: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients., [Methods]: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes., [Results]: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening., [Conclusion]: Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed., Funded by grants PI14–01495 and PI17–01401 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain supported by FEDER funds) and by one ACCI project from CIBERER and one grant to the FPI cohort from CIBERES., We acknowledge support of the publication fee by the CSIC Open Access Publication Support initiative through its Unit of Information Resources for Research (URICI).

Introduction Pulmonary fibrosis (PF) and its most common form, idiopathic pulmonary fibrosis (IPF), are chronic, progressive diseases resulting in increasing loss of lung function and impaired quality of life and survival. The aim of this joint expert and patient statement was to highlight the most pressing common unmet needs of patients with PF/IPF, putting forward recommendations to improve the quality of life and health outcomes throughout the patient journey. Methods Two online surveys for patients and healthcare professionals (HCPs) were conducted by the European Idiopathic Pulmonary Fibrosis and Related Disorders Federation (EU-IPFF) in 14 European countries. Results The surveys were answered by 286 patients and 69 HCPs, including physicians and nurses. Delays in diagnosis and timely access to interstitial lung disease specialists and pharmacological treatment have been identified as important gaps in care. Additionally, patients and HCPs reported that a greater focus on symptom-centred management, adequate information, trial information and increasing awareness of PF/IPF is required. Conclusions The surveys offer important insights into the current unmet needs of PF/IPF patients. Interventions at different points of the care pathway are needed to improve patient experience., This joint expert and patient statement highlights the most pressing common unmet needs of patients with pulmonary fibrosis, and puts forward recommendations to improve the quality of life and health outcomes throughout the patient journey http://bit.ly/34cTOeo

Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited knowledge regarding prevalence in routine practice. We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions via society and collaborators networks. Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings. An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations., In real-world practice, ILD diagnosis uses a multidisciplinary team approach, irrespective of country or healthcare setting http://ow.ly/I1Di30nMNTX

Background: Previous reports showed an imbalance of the soluble receptor for advanced glycation end-products (sRAGE), an immunoglobulin implicated in the maintenance of alveolar structures, with its ligand (AGE), in lung samples from idiopathic pulmonary fibrosis (IPF). The finding of a non-invasive serum biomarker would help in the early diagnosis and prognosis of IPF and would distinguish it from other fibrotic interstitial lung diseases, such as fibrotic nonspecific interstitial pneumonia (fNSIP) or chronic hypersensitivity pneumonitis (cHP). Aims: We analysed the role of AGE and RAGE levels and the ratio of both molecules in serum samples as possible biomarkers that distinguish different fibrotic interstitial lung entities. Method: Serum samples were collected from 48 IPF patients, 15 cHP, 15 fNSIP, and 12 healthy age matched controls. Patient characteristics (age, sex, smoke habits, and pulmonary functional test (PFT)) were recorded. AGEs and sRAGE level were assessed by ELISA following the manufacture’s recommendation. Patient’s data and serum determinations were analysed with SPSS statistic software. Results: Our study demonstrated a decrease in sRAGE together with an increment of AGEs levels in serum in IPF and cHP samples compared with control and fNSIP, which did not show significant differences between them. AGEs levels resulted negative correlated with sRAGE in IPF samples. Moreover, low levels of sRAGE correlates with worse PFT (FVC and DLCO). Conclusions: This findings demonstrate that the imbalance in AGE/sRAGE levels in serum samples could differentiate IPF and cHP from NSIP. Furthermore, the correlation between sRAGE measurements and patient’s PFT could reflect the severity of the disease.

Background and objective Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease of unknown etiology. The diagnosis is based on the identification of a pattern of usual interstitial pneumonia either by high resolution computed tomography and/or histology. However, a similar pattern can be observed in other fibrotic lung disorders, and precise diagnosis remains challenging. Studies on biomarkers contributing to the differential diagnosis are scanty, and still in an exploratory phase. Our aim was to evaluate matrix metalloproteinase (MMP)-28, which has been implicated in abnormal wound healing, as a biomarker for distinguishing IPF from fibrotic non-IPF patients. Methods The cell localization of MMP28 in lungs was examined by immunohistochemistry and its serum concentration was measured by ELISA in two different populations. The derivation cohort included 82 IPF and 69 fibrotic non-IPF patients. The validation cohort involved 42 IPF and 41 fibrotic non-IPF patients. Results MMP28 was detected mainly in IPF lungs and localized in epithelial cells. In both cohorts, serum concentrations of MMP28 were significantly higher in IPF versus non-IPF (mostly with lung fibrosis associated to autoimmune diseases and chronic hypersensitivity pneumonitis) and healthy controls (ANOVA, p

Background The soluble receptor for advanced glycation end-products (sRAGE) has been suggested that it acts as a decoy for capturing advanced glycation end-products (AGEs) and inhibits the activation of the oxidative stress and apoptotic pathways. Lung AGEs/sRAGE is increased in idiopathic pulmonary fibrosis (IPF). The objective of the study was to evaluate the AGEs and sRAGE levels in serum as a potential biomarker in IPF. Methods Serum samples were collected from adult patients: 62 IPF, 22 chronic hypersensitivity pneumonitis (cHP), 20 fibrotic non-specific interstitial pneumonia (fNSIP); and 12 healthy controls. In addition, 23 IPF patients were re-evaluated after 3-year follow-up period. Epidemiological and clinical features were recorded: age, sex, smoking habits, and lung function. AGEs and sRAGE were evaluated by ELISA, and the results were correlated with pulmonary functional test values. Results IPF and cHP groups presented a significant increase of AGE/sRAGE serum concentration compared with fNSIP patients. Moreover, an inverse correlation between AGEs and sRAGE levels were found in IPF, and serum sRAGE at diagnosis correlated with FVC and DLCO values. Additionally, changes in serum AGEs and sRAGE correlated with % change of FVC, DLCO and TLC during the follow-up. sRAGE levels below 428.25 pg/ml evolved poor survival rates. Conclusions These findings demonstrate that the increase of AGE/sRAGE ratio is higher in IPF, although the levels were close to cHP. AGE/sRAGE increase correlates with respiratory functional progression. Furthermore, the concentration of sRAGE in blood stream at diagnosis and follow-up could be considered as a potential prognostic biomarker. Electronic supplementary material The online version of this article (10.1186/s12931-018-0924-7) contains supplementary material, which is available to authorized users.

The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications.Consecutive Spanish patients were included at diagnosis and followed up for 3 years. DNA blood samples from a Mexican cohort were used to validate the results found in Spanish sporadic IPF. Prior to treatment, telomere length was measured through quantitative polymerase chain reaction (qPCR) and Southern blot. Outcome was assessed according to mortality or need for lung transplantation. A multivariate regression logistic model was used for statistical analysis.Family aggregation, age of60 years and the presence of non-specific immunological or haematological abnormalities were associated with a higher probability of telomere shortening. Overall, 66.6% of patients younger than 60 years with telomere shortening died or required lung transplantation, independent of functional impairment at diagnosis. By contrast, in patients older than 60 years with telomere shortening, the negative impact of telomere shortening in outcome was not significant.Our data indicate that young sporadic IPF patients (60 years) with some non-specific immunological or haematological abnormalities had higher risk of telomere shortening, and furthermore, they presented a poorer prognosis.

Introduction: The expert multidisciplinary (MDT) approach is crucial for the accurate diagnosis of interstitial lung diseases (ILD), however the presence of this MDT is not always possible in centers with ILD management. Objectives: To evaluate the relevance of each disciplinary approach (clinical, biochemical, radiological, histological) included in the MDT assessment of ILD patients. Methods: Prospective observational study of all first visits evaluated in the ILD Unit during 2014. The assessment was determined by; A-1) detailed history, complete autoimmunity and precipitin, genetic study to family suspected, A-2) identifying radiological pattern of chest tomography (HRCT) by two independent radiologists, A-3) Pathology, A-4): MDT committee discussion (cases in which A1+/- A2 or A3 did not reach the diagnosis). Results: From the included 158 cases (89 men, mean age 64.4 years), 77 patients were referred from primary care centers and local hospitals. The median time from the visit request to the diagnosis was 4.97 months (IQR 7.8). 91 had an initial diagnosis, which was modified in 18 cases: 3 by A-1, 1 by A-3, 5 by A-4, 9 by A-1+A-2. The final diagnosis was obtained in 149 cases. From the 9 patients with no diagnosis: 6 had advanced age and/or comorbidities, and 3 by low diagnostic yield of lung biopsy (incipient disease). A-4 was made in 23 cases (14.6%). 48 samples of lung pathology were analyzed (31 surgical biopsy and 17 cryobiopsy). Conclusions: The MDT committee discussion is mandatory in almost one third of cases for the final diagnosis. An exhaustive clinical and serological study together with an expert radiological evaluation is the most effective requirement to manage ILD patients.

Introduction: Recent studies suggest a link between advanced glycation end-products (AGEs) and their receptors (RAGE) with the physiopathology of pulmonary fibrosis. AGEs are implicated in oxidative stress reactions. Objectives: To evaluate RAGE and AGEs expression and location in normal and fibrotic lungs and their role in idiopathic pulmonary fibrosis (IPF). Methods: Fibrotic lung samples (n=16) were obtained from IPF patients that underwent to surgical lung biopsy for diagnosis. Histology showed a usual interstitial pneumonia (UIP) pattern in all samples. Control lung samples (n=9) were obtained from distal areas of lung cancer segment resections. RAGE expression from tissue homogenates were assessed by PCR and immunoblot, and AGEs detection was evaluated by western blot. The specific cell type distribution was analysed by immunohistochemistry. Results: RAGE protein and mRNA expression were decreased in IPF patients compared to control samples (p Conclusions: These findings confirm a downregulation of RAGE together with an increase of AGEs in IPF tissues. This AGE/RAGE imbalance could be implicated in abnormal remodeling and alveolar epithelial cell repair in the pathogenesis of lung fibrosis.