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Background and aims This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn’s disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. Methods In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. Results CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (p Conclusions We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD.

Methods We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18?80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40?90% predicted, a diffusing capacity of the lung for carbon monoxide of 10?90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6?24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebocontrolled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32;Background Pirfenidone has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). However, there are few treatment options for progressive fibrotic interstitial lung diseases (ILDs)) other than IPF. In view of the pathomechanistic and clinical similarities between IPF and other progressive fibrotic ILDs, we aimed to assess the efficacy and safety of pirfenidone in patients with four non-IPF progressive fibrotic ILDs. Methods We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18-80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40-90% predicted, a diffusing capacity of the lung for carbon monoxide of 10-90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6-24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebo controlled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32; DRKS00009822 and is no longer recruiting. Findings Between April 5, 2016, and Oct 4, 2018, we randomly assigned 127 patients to treatment: 64 to pirfenidone, 63 to placebo. After 127 patients had been randomised, the study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks and in the overall population of 127 patients, rank ANCOVA with diagnostic group included as a factor showed a significantly lower decline in FVC % predicted in the pirfenidone group compared with placebo (p=0.043); the result was similar when the model was stratified by diagnostic group (p=0.042). A significant treatment effect was also observed when applying the LOCF and multiple imputation methods to analyses of the primary endpoint.The median difference (Hodges-Lehmann estimate) between pirfenidone and placebo groups for the primary endpoint was 1.69 FVC % predicted (95% CI -0.65 to 4.03). In the linear mixed-model repeated measures slope analysis of FVC % predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3.53 FVC % predicted (95% CI 0.21 to 6.86) with imputation of deaths as prespecified, or 2.79 FVC % predicted (95% CI 0.03 to 5.54) without imputation. One death (non-respiratory) occurred in the pirfenidone group (2%) and five deaths (three of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (five [8%] in the pirfenidone group, ten [16%] in the placebo group); general disorders including disease worsening (two [3%] in the pirfenidone group, seven [11%] in the placebo group); and cardiac disorders (one ([2%] in the pirfenidone group, 5 [8%] in the placebo group). Adverse events (grade 3-4) of nausea (two patients on pirfenidone, two on placebo), dyspnoea (one patient on pirfenidone, one on placebo), and diarrhoea (one patient on pirfenidone) were also observed. Interpretation In view of the premature study termination, results should be interpreted with care. Nevertheless, our data suggest that in patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment might attenuate disease progression as measured by decline in FVC. Funding German Center for Lung Research, Roche Pharma.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic pulmonary disease with rising incidence. In this study the effectiveness of pirfenidone, as measured by longitudinal change in individual slope of forced vital capacity (FVC) prior to and after initiating pirfenidone treatment, was evaluated in IPF patients recruited into the European registry for idiopathic pulmonary fibrosis (eurIPFreg). Secondary variables were the evaluation of the change in individual slope of diffusion capacity of the lungs for carbon monoxide (DLco), the Borg dyspnea scale, and six-minute walking distance (6MWD), as well as survival analyses. Results: Data of 122 eurIPFreg patients, who had at least two pulmonary function tests (PFTs) prior to or under treatment with pirfenidone, were analyzed by calculating slope-changes. The global analysis revealed an average slope change of +1.48 &plusmn, 0.28 (% per annum (p.a)) after start of treatment (p &lt, 0.001), reflecting a reduction in annual FVC decline of approx. 50% under pirfenidone, it also showed a reduction in DLco, and increase in 6MWD (both p &lt, 0.0001), as well as a flattening of the Borg dyspnea scale (p = 0.02). The median survival under treatment was 4.82 years. Patients with a more restrictive disease (FVC &lt, 80% pred.), with a rapid progression (FVC decline &gt, 10% pred. p.a.), previous smokers and patients &gt, 60 years of age seemed to profit more from pirfenidone treatment. Conclusions: We report the effectiveness of pirfenidone in a European &ldquo, real world&rdquo, IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time. Survival was dependent on Gender&ndash, Age&ndash, Physiology (GAP) score and age prior to therapy.

Background: Longitudinal response to treatment with pirfenidone is highly variable. This study evaluated the effectiveness of pirfenidone, as measured by longitutidal changes in FVC (% pred.), DLco (% pred), Borg dyspnoe scale, and six minute walking distance test, as well as survival analyses. Methods: Data were available for 122 eurIPFreg patients. Patients’ data from at least two subsequent records with/without antifibrotic treatment were analyzed by slope-changes in each individual patient, as well as in global analysis, where the data from all patients were used to fit a global segmented regression model. Results: The individual analysis showed a tremendous heterogeneity, and the mean FVC slope difference was not significantly different from baseline (p = 0.32). The global analysis revealed an average slope change of +1.48 (% p.a.) ± 0.28 (p Conclusions: We report the effectiveness of pirfenidone in European IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time.

Background: Despite novel treatment options, idiopathic pulmonary fibrosis (IPF) still shows a progressive and fatal course. In search for further parameters of disease progression, we studied the role of Tidal Volume (VT), alongside with established risk factors such as FVC or GAP index. Aim and Methods: We analyzed 266 IPF patients recruited in Giessen und Paris into the eurIPFreg for baseline data, change in VT or other lung function values, and intake of antifibrotics (AF) for a follow up period of up to ten years. The estimated effects of VT on the hazard ratio (HR) were adjusted by sex, age at t0, smoking status, AF, ideal body weight and GAP score at t0. Results: The cohort showed the following demographics: 80.6% males, mean age at t0 67.8 years, FVC 64.7% pred., 77.4% active or previous smokers. VT correlated significantly with VC % pred., FVC % pred., pH and pCO2. A survival analysis revealed a highly significant impact of GAP score on survival, higher in the group under AF. VT also exerted significant effects on survival; every 100ml increase in the baseline VT was associated with a predicted decrease of the HR by a factor of 0.84 and a correspondingly improved survival. There was no clear evidence for a protective effect of very low TV. Conclusions: In IPF subjects, multiple factors affect outcome, among these are GAP index, smoking, antifibrotic treatment, and also VT. Against our anticipation, very low VTs were not associated with improved outcome, most likely because baseline VT is impacted by FVC and, hence, the extent of fibrotic disease.

(1) Aim of the study: In spite of extensive research, up to 20% of interstitial lung diseases (ILD) patients cannot be safely classified. We analyzed clinical features, progression factors, and outcomes of unclassifiable ILD (uILD). (2) Methods: A total of 140 uILD subjects from the University of Giessen and Marburg Lung Center (UGMLC) were recruited between 11/2009 and 01/2019 into the European Registry for idiopathic pulmonary fibrosis (eurIPFreg) and followed until 01/2020. The diagnosis of uILD was applied only when a conclusive diagnosis could not be reached with certainty. (3) Results: In 46.4% of the patients, the uILD diagnosis was due to conflicting clinical, radiological, and pathological data. By applying the diagnostic criteria of usual interstitial pneumonia (UIP) based on computed tomography (CT), published by the Fleischner Society, 22.2% of the patients displayed a typical UIP pattern. We also showed that forced vital capacity (FVC) at baseline (p = 0.008), annual FVC decline ≥10% (p < 0.0001), smoking (p = 0.033), and a diffusing capacity of the lung for carbon monoxide (DLco) ≤55% of predicted value at baseline (p < 0.0001) were significantly associated with progressive disease. (4) Conclusions: The most important prognostic factors in uILD are baseline level and decline in lung function and smoking. The use of Fleischner diagnostic criteria allows further differentiation and accurate diagnosis.

There is a high unmet need in a non-invasive screening of lung cancer (LC). We conducted this single-center trial to evaluate the effectiveness of the electronic nose AeonoseExhaled volatile organic compound (VOC) signatures were collected by AeonoseThe established algorithm of AeonoseThe Aeonose(NCT02951416).

This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn's disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (p 0.01), psychological distress (p 0.001) and maladaptive stress coping (escape, p = 0.03; rumination, p 0.03), but less need for social support (p = 0.001) than controls. In contrast, patients suffering from active UC showed psychological distress (p 0.04) and maladaptive coping (avoidance, p 0.03; escape, p = 0.01). Patients in remission seemed to be less affected. In particular, patients with UC in remission were not inflicted by psychological impairments. The group of CD patients in remission however, showed insecurity (p 0.01) and paranoid ideation (p = 0.04). We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD. Diese Studie untersuchte Unterschiede in der Persönlichkeit, psychische Belastung und Stressbewältigung bei chronisch-entzündlichen Darmerkrankungen (CED) in Abhängigkeit von der Art der Erkrankung und der Krankheitsaktivität. Wir verglichen Patienten mit Morbus Crohn (CD) und Colitis ulcerosa (UC) mit Kontrollgruppen. Während die Literatur zu charakteristischen Merkmalen der Pathogenese von IBD zahlreich ist, sind die spezifischen Unterschiede in den psychischen Beeinträchtigungen nicht ausreichend untersucht. In dieser deutschen nationalen Multicenterstudie wurden Teilnehmer aus 32 Zentren rekrutiert. Es wurden 297 Fragebögen mit umfassenden Informationen über den Krankheitsstatus und das psychische Wohlbefinden auf der Grundlage validierter psychosozialer Instrumente mit insgesamt 285 Items evaluiert. CD-Patienten waren stärker von psychischen Beeinträchtigungen betroffen als Patienten mit UC oder Kontrollen. Wichtig ist, dass Patienten mit aktiver CD in den Bereichen Neurotizismus (p 0,01), psychische Belastung (p 0,001) und maladaptive Stressbewältigung (p 0,03) höhere Werte, aber weniger Bedarf für soziale Unterstützung (p = 0,001) als Kontrollen aufwiesen. Im Gegensatz dazu zeigten Patienten, die an aktiver UC litten, psychische Belastung (p 0,04) und maladaptive Coping (Vermeidung, p 0,03; Flucht, p = 0,01). Patienten in Remission schienen weniger betroffen zu sein. Die Gruppe der CD-Patienten in Remission zeigte jedoch Unsicherheit (p 0,01). Wir identifizierten spezifische Aspekte der psychischen Beeinträchtigung bei IBD abhängig von Krankheit und Krankheitsaktivität. Unsere Ergebnisse untermauern den Bedarf an psychologischer Unterstützung und Behandlung, insbesondere bei aktiver CD.

International audience; Objectives: There is a high unmet need in a non-invasive screening of lung cancer (LC). We conducted this single-center trial to evaluate the effectiveness of the electronic nose Aeonose ® in LC recognition.Materials and methods: Exhaled volatile organic compound (VOC) signatures were collected by Aeonose ® in 42 incident and 78 prevalent LC patients, of them 29 LC patients in complete remission (LC CR), 33 healthy controls (HC) and 23 COPD patients. By dichotomous comparison of VOC's between incident LC and HC, a discriminating algorithm was established and also applied to LC CR and COPD subjects. Area under Curve (AUC), sensitivity, specificity and Matthews's correlation coefficient (MC) were used to interpret the data.Results: The established algorithm of Aeonose ® signature allowed safe separation of LC and HC, showing an AUC of 0.92, sensitivity of 0.84 and a specificity of 0.97. When tested in a blinded fashion, the device recognized 19 out of 29 LC CR patients (=65.5%) as LC-positive, of which only five developed recurrent LC later on (after 18.6 months [Formula: see text]; mean value [Formula: see text]). Unfortunately, the algorithm also recognized 11 of 24 COPD patients as being LC positive (with only one of the 24 COPD patients developing LC 56 months after the measurement).Conclusion: The Aeonose ® revealed some potential in distinguishing LC from HC, however, with low specificity when applying the algorithm in a blinded fashion to other disease cohorts. We conclude that relevant VOC signals originating from comorbidities in LC such as COPD may have erroneously led to the separation between LC and controls.Clinical trial registration: (NCT02951416).

Background and Aims: This study analysed relative frequency, clinical characteristics, disease onset and progression in f-IPF vs. sporadic IPF (s-IPF) in a cohort of patients recruited into the eurIPFreg at our UGMLC sites in Giessen and Greifenstein. Methods: The f-IPF index patients and their families were retrospectively analysed. Employing wide range criteria of fam. IPF (e.g. relatives who presumably died of some kind of DPLD), 60 index patients were identified. Taken occurrence of either NSIP or IPF in one first grade relative, 28 index patients were finally identified and prospectively interviewed and examined, inkl. blood samples and pedigrees. Results: In the 28 IPF families, overall 79 patients with f-IPF were found (incl.index patients), corresponding to a relative portion of f-IPF vs. s-IPF of 19%. The f-IPF group differed by an earlier age at the onset of the disease (55.4 vs. 63.2 years; p≤0.001); f-IPF patients reported more frequently on persistent, dry cough, vs. s-IPF group (p Conclusions: The 28 f-IPF patients showed an earlier onset and more aggressive natural course of the disease vs. s-IPF. The disease seems to affect the following generation at a younger age.

Background In this study, we retrospectively assessed the relationships among physiologic measurements, survival, and quantitative high-resolution CT (HRCT) scanning indexes in patients with idiopathic pulmonary fibrosis (IPF). Methods Seventy patients (48 male; mean [SD] age, 66.4 [9.0] years) with IPF were enrolled in the study. After segmentation of the lungs in thin-section CT scanning with the patient in the supine position at full inspiration, we assessed following parameters: mean lung attenuation (MLA), skewness, kurtosis, peak attenuation, total lung area, inflexion point with slope, and area right of the inflexion point (AROIP). Additionally, FVC, FEV1, total lung capacity, diffusing capacity or transfer factor of the lung for carbon monoxide (Dlco), and 6-min walk distance were analyzed. Univariate and multivariate analysis were used for the prediction of physiologic outcomes by HRCT scanning indexes and then were correlated to survival in a proportional hazards analysis. Results The strongest correlation was observed between MLA and FEV1, with an r of −0.63. MLA, peak attenuation, slope, attenuation, and AROIP correlated negatively with all physiologic measurements. AROIP was the best predictor of Dlco. Analysis for prediction of mortality showed that AROIP, kurtosis, and FVC were related significantly to survival. Multivariate regression revealed a significant impact of only AROIP (among age, sex, MLA, skewness, kurtosis, FVC, and Dlco) on survival. Conclusions These data indicate that HRCT scanning indexes are correlated to physiologic measurements. The newly defined parameter, AROIP, is of additive value for prediction of outcome. Trial Registry ClinicalTrials.gov; No.: NCT02951416; URL: www.clinicaltrials.gov

Background Idiopathic pulmonary fibrosis (IPF) is a rare disease with a median survival of 3–5 years after diagnosis with limited treatment options. The aim of this study is to assess the psychometric characteristics of the Short Form 36 Health Status Questionnaire (SF-36) in IPF and to provide disease specific minimally important differences (MID). Methods Data source was the European IPF Registry (eurIPFreg). The psychometric properties of the SF-36 version 2 were evaluated based on objective clinical measures as well as subjective perception. We analysed acceptance, feasibility, discrimination ability, construct and criterion validity, responsiveness and test-retest-reliability. MIDs were estimated via distribution and anchor-based approaches. Results The study population included 258 individuals (73.3% male; mean age 67.3 years, SD 10.7). Of them 75.2% (194 individuals) had no missing item. The distribution of several items was skewed, although floor effect was acceptable. Physical component score (PCS) correlated significantly and moderately with several anchors, whereas the correlations of mental component score (MCS) and anchors were only small. The tests showed mainly significant lower HRQL in individuals with long-term oxygen therapy. Analyses in stable individuals did not show significant changes of HRQL except for one dimension and anchor. Individuals with relevant changes of the health status based on the anchors had significant changes in all SF-36 dimensions and summary scales except for the dimension PAIN. PCS and MCS had mean MIDs of five and six, respectively. Mean MIDs of the dimensions ranged from seven to 21. Conclusion It seems that the SF-36 is a valid instrument to measure HRQL in IPF and so can be used in RCTs or individual monitoring of disease. Nevertheless, the additional evaluation of longitudinal aspects and MIDs can be recommended to further analyse these factors. Our findings have a great potential impact on the evaluation of IPF patients. Trial registration The eurIPFreg and eurIPFbank are listed in https://clinicaltrials.gov (NCT02951416). Electronic supplementary material The online version of this article (10.1186/s12931-019-1010-5) contains supplementary material, which is available to authorized users.

Background: The survival in LC strictly depends on the stage and the timepoint of diagnosis; thus an early detection of disease is crucial. The Aeonose® as a non-invasive test is of longstanding interest for detection of LC. Methods: In total, signatures of exhaled volatile compounds (VOCs) of 30 incident and untreated prevalent LC patients, who did not smoke in the last 2hrs prior to measurement, were captured via Aeonose® vs. 25 healthy subjects (HC). Area under Curve (AUC) and Matthews coefficient (MC) were used to interpret the data. Results: The Aeonose® differed in direct comparison between patients with LC and HC (n=25), showing an AUC of 0.95 and MC of 0.85. By validating the ability of Aeonose® to recognize a sustained LC remission or to predict relapse, we put the group LC complete remission (CR) into data statistics as blind samples. Interestingly, the device recognized all 25 CR patients as LC-positive. Indeed, 3/25 patients developed a cancer over the time after a measurement. To confirm these results further, we put 24 COPD patients as blind data, which were recognized by Aeonose® as LC positive as well. Conclusions: The Aeonose® shows some potential in identifying different LC cases. In our study, however, the device did not identify LC CR patients as cancer-negative. Our data suggest that – based on the current approach of comparing always only two conditions - relevant VOC signals originating from comorbidities such as COPD may have erroneously led to separation between LC and control. To overcome this, a multivariate approach or strategies following the concept of principal compound analysis, should be applied in future, cross-sectional studies.

Background: There is an increasing interest in employing electronic nose technology in the diagnosis and monitoring of lung diseases. Interstitial lung diseases (ILD) are challenging in regard to setting an accurate diagnosis in a timely manner. Thus, there is a high unmet need in non-invasive diagnostic tests. This single-center explorative study aimed to evaluate the usefulness of electronic nose (Aeonose&reg, ) in the diagnosis of ILDs. Methods: Exhaled volatile organic compound (VOC) signatures were obtained by Aeonose&reg, in 174 ILD patients, 23 patients with chronic obstructive pulmonary disease (COPD), and 33 healthy controls (HC). Results: By dichotomous comparison of VOC&rsquo, s between ILD, COPD, and HC, a discriminating algorithm was established. In addition, direct analyses between the ILD subgroups, e.g., cryptogenic organizing pneumonia (COP, n = 28), idiopathic pulmonary fibrosis (IPF, n = 51), and connective tissue disease-associated ILD (CTD-ILD, n = 25) were performed. Area under the Curve (AUC) and Matthews&rsquo, s correlation coefficient (MCC) were used to interpret the data. In direct comparison of the different ILD subgroups to HC, the algorithms developed on the basis of the Aeonose&reg, signatures allowed safe separation between IPF vs. HC (AUC of 0.95, MCC of 0.73), COP vs. HC (AUC 0.89, MCC 0.67), and CTD-ILD vs. HC (AUC 0.90, MCC 0.69). Additionally, to a case-control study design, the breath patterns of ILD subgroups were compared to each other. Following this approach, the sensitivity and specificity showed a relevant drop, which results in a poorer performance of the algorithm to separate the different ILD subgroups (IPF vs. COP with MCC 0.49, IPF vs. CTD-ILD with MCC 0.55, and COP vs. CT-ILD with MCC 0.40). Conclusions: The Aeonose&reg, showed some potential in separating ILD subgroups from HC. Unfortunately, when applying the algorithm to distinguish ILD subgroups from each other, the device showed low specificity. We suggest that artificial intelligence or principle compound analysis-based studies of a much broader data set of patients with ILDs may be much better suited to train these devices.

Background & aims: Ileo-colonic strictures are common complication of Crohn’s disease (CD), and may result in repeated endoscopic or surgical therapy with a risk of further complications, such as perforation or short bowel syndrome. Strictures develop as a consequence of tissue remodelling and fibrosis due to chronic inflammation. This study compares the outcome of CD patients undergoing primarily endoscopic treatment with those undergoing surgery at an university hospital. Methods: In this study we retrospectively included 88 CD patients with intestinal strictures (37 males, 51 females, mean age 40 years, range 19-65 years) of both our medical and our surgical department, who underwent either surgical or endoscopic therapy between January 2002 and January 2006 with prospective, controlled follow-up, extended till January 2010 (mean follow-up period: 5 years; range 4-8 years). The primary end-point was operation- and symptom-free time. Patients were primarily divided into four groups: only surgical therapy, only endoscopic therapy, endoscopy with subsequent surgery, and initial surgical therapy followed by endoscopic dilations. Results: 53% of all patients remained surgery-free with mean follow-up of 49 months; a single endoscopic dilation was sufficient enough in 9 patients to achieve a surgery-free time of 51 months, other patients required up to 5 dilations. The average interval between first and second dilation was 6.5 months, between second and third 10.5 months. In the group of patients with only endoscopic therapy, surgery- and symptom-free time was shorter, as compared to the group of only surgical therapy. We found that stenoses in the surgical group with an average length of 6.5 cm were as expected longer, as compared to the endoscopic group (3 cm, ranging from 2-4 cm). The surgery-free time was 49 months (42-71 months, P = 0.723) with a symptom-free time of 12 months (4.5-46 months, P = 0.921). In the group of only surgically treated patients, 68.4% of the patients had only one stenosis, 18.4% had 2-3 stenoses and 13.2% more than 3 stenoses. In all patients the surgery- and symptoms- free time was 69 months (57-83 months, P = 0.850 and 0.908). The other two groups showed similar results. We found no significant effect of characteristic of stenosis (length, inflammation, the number of stenoses), injection of prednisolone, disease activity at the time of dilation and medication at the time of dilation on the long-term outcome. Importantly, the success of symptom free time correlated with the diameter of the balloon. Conclusions: Endoscopic dilation should be considered as a first-line therapy for short, accessible, fibrotic strictures. Careful patient selection and proper diagnostic imaging pre-procedure are essential requirements for safe and successful treatment. The balloon diameter seems to correlate positively with the long term outcome of dilation. However, at ever shorter intervals between endoscopic interventions, surgery should be discussed as an option for further treatment.

Clinical observations suggest that the lymphoid follicles (LFs) may play a crucial role in the pathogenesis of inflammatory bowel disease (IBD), especially in Crohn's disease (CD) as the site of initial mucosal inflammation. The aim of this study was to compare the morphology of LFs in CD, ulcerative colitis (UC) and control patients using confocal laser endomicroscopy (CLE) in correlation to histological and immunohistochemical findings of biopsies.79 patients with IBD (46 with CD, 32 with UC and 1 patient with indeterminate colitis) and 67 controls patients were enrolled prospectively in this study. Median age was 32.5 years (range 19-65) and 37.4 years (range 20-65 years) respectively. To analyze the LFs, standardized images from the terminal ileum and the colon were taken using white-light video endoscopes. Additionally, CLE was performed to analyze subsurface structure of LFs. Targeted biopsies of LFs were analyzed using haematoxylin and eosin stain and immunohistochemistry.LFs were seen in all parts of the lower GI tract, but mostly in the terminal ileum and cecum. Endoscopy in 15 out of 17 patients with the first manifestation of CD showed LFs surrounded by red ring (so-called red ring sign, RRS). Histologically, LFs with RRS showed hypervascularization at the base of the LFs associated with numerous CD15-positive granulocytes. Similar features were not seen in LFs without RRS and in the control group. In some LFs with RRS early aphthous ulcers were seen. Using CLE, RRS showed abolished normal crypt architecture, crypt distortion, increased cellular infiltrate within the lamina propria, and dilated vessels.LFs with RRS probably represent an early sign of aphthous ulcers in early CD and, thus, may be considered as early markers of first manifestation and flares in CD.