Search

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that takes an airway segmentation and CT image as input and systematically parcellates the airway tree into its lobes and generational branches, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent.

Abstract Background Advanced pulmonary sarcoidosis causes significant morbidity and can lead to death. Large trials demonstrated efficacy of antifibrotics in patients with progressive fibrosing interstitial lung diseases (PF-ILD), including a few with sarcoidosis. To date, little is known about this progressive fibrosing phenotype in sarcoidosis. Diffusion capacity of carbon monoxide (DLCO) may be a useful functional marker to screen for advanced pulmonary sarcoidosis. In this study, we describe a cohort with advanced pulmonary sarcoidosis and we gain insights in the progressive fibrosing phenotype in sarcoidosis. Methods Patients with sarcoidosis and a DLCO 10% fibrosis on HRCT meeting the criteria for ILD-progression within 24 months were labelled as PF-ILD. With Cox-regression analysis predictors of mortality were established. Results 106 patients with a DLCO 10% fibrosis on HRCT. Independent predictors of mortality and lung transplantation in the whole cohort are PH, PF-ILD and UIP-like pattern. Conclusion In conclusion, within this group with advanced pulmonary sarcoidosis disease course varied widely from great functional improvement to death. PF-ILD patients had higher mortality rate than the mortality in the overall pulmonary sarcoidosis group. Future research should focus on the addition of antifibrotics in these patients. Trial registration retrospectively registered

Abstract Background Involvement of metals or silica in the pathogenesis of sarcoidosis has been suggested by several case reports and specific epidemiological studies. However, the combination of occupational exposure and an immunological reaction has not been studied before in a group of sarcoidosis patients and non-sarcoidosis controls. Methods In 256 sarcoidosis patients and 73 control patients with obstructive sleep apnea, exposure to metal and silica was assessed using a questionnaire consisting of a complete occupational history subsequently linked to job-exposure matrices. Next, immunoreactivity to aluminium, beryllium, zirconium and silica was determined in 33 sarcoidosis and 19 control patients using a lymphocyte proliferation test. Results In sarcoidosis, 83 out 256 patients (32.4%) had occupational exposure to metals or silica, compared to 24.7% in the control group (p = 0.21). A significantly higher percentage of the sarcoidosis patients tested showed immunoreactivity to metals or silica compared to the control group (21.2 and 0% respectively, p = 0.039). Conclusions Immunoreactivity to silica and metals was only found in sarcoidosis patients, supporting the hypothesis that these antigens may be involved in the pathogenesis of a distinct subgroup of sarcoidosis patients. This indicates that when searching for causative agents in sarcoidosis patients, besides beryllium, also zirconium, aluminium and silica deserve clinical investigation.

Autoimmune pulmonary alveolar proteinosis (aPAP), which accounts for >90% of all cases of PAP, is a rare lung disease mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies that block GM-CSF signalling, leading to reduced surfactant clearance causing abnormal accumulation of alveolar surfactant and impaired gas exchange [1-3]. The current standard of care for aPAP is whole-lung lavage (WLL), which is invasive, resource intensive, carries procedural risk, does not address the underlying cause of disease and often must be repeated regularly [4]. Hence, there is a therapeutical need to address the underlying pathophysiology of the disease. Studies have explored inhaled GM-CSF augmentation as a primary treatment for aPAP [5-12]. In this real-world case series, we present the beneficial long-term effects of molgramostim inhalation solution, an investigational, recombinant GM-CSF, in five aPAP patients with therapeutic disease challenges., Competing Interests: Conflict of interest: C. Montaño reports receiving support for the present manuscript from Savara. Conflict of interest: E. Bendstrup reports receiving support for the present manuscript from Savara; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer Ingelheim, Hofmann la Roche, Daiichi-Sankyo and AstraZeneca, outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, Veracyte and Simbec, outside the submitted work. Conflict of interest: I. Rønnov-Jessen reports receiving support for the present manuscript from Savara. Conflict of interest: S. Salgado reports receiving support for the present manuscript from Savara. Conflict of interest: G. Sterniste reports receiving support for the present manuscript from Savara. Conflict of interest: A. Valipour reports receiving support for the present manuscript from Savara. Conflict of interest: M. Veltkamp reports receiving support for the present manuscript from Savara. Conflict of interest: M. Molina-Molina reports receiving support for the present manuscript from Savara; grants received from Boehringer Ingelheim outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Boehringer Ingelheim, Roche, Ferrer and Janssen, outside the submitted work; and support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work., (Copyright ©The authors 2025.)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrosing lung disease. A decreased 6-min walk distance (6MWD) and exercise-induced oxygen desaturation measured during the 6-min walk test (6MWT), are known predictors of mortality in patients with IPF. However, the use of antifibrotic drugs showed a survival benefit in IPF. Therefore, this study aimed to evaluate to what extend 6MWT-derived attributes are associated with two-year survival when antifibrotic drugs were introduced as part of standard IPF-care., Methods: This real-world data-study included patients with IPF with a 6MWT between 2015 and 2020, and used composite outcome: mortality or lung transplantation within 2 years of follow-up. Data were collected systematically, including demographics, pulmonary function tests, comorbidities, medications and 6MWT-derived attributes. The prediction attributes of 6MWT were studied with a Cox Proportional-Hazards model and Kaplan-Meier survival curves. The best discriminating attribute to predict mortality was added to the prediction model Gender-Age-Physiology (GAP)., Results: In 216 patients, 2-year transplant-free survival cut-off points were identified for the 6MWD (≥413 m), 6MWD %predicted (≥83 %), SpO 2 -nadir (≥86 %) and distance-saturation-product (≥374 m%), with the best discriminative value for SpO 2 -nadir (area under the curve: 0.761). 2-Year survival percentage of patients with SpO 2 -nadir below or above threshold (86 %) was 37.1 % and 80.0 %, respectively. Exercise-induced oxygen desaturation added to the GAP model showed an improvement in its predictive power., Conclusion: Patients with IPF who have an exercise-induced oxygen desaturation have worse prognosis. Addition of SpO 2 -nadir to the GAP model seems promising for use in clinical care of IPF patients., Competing Interests: Declaration of competing interest The author declares on behalf of all authors that they have no relevant or material financial interests related to the research described in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Early detection of cardiac sarcoidosis (CS) is crucial due to its association with severe complications such as ventricular arrhythmias, heart failure, and sudden cardiac death. Advanced imaging techniques like cardiac magnetic resonance imaging (CMR) and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) are effective in detecting CS but not easily accessible. The optimal method for selecting patients for advanced screening remains uncertain., Methods: In this retrospective cohort study, all extracardiac sarcoidosis patients screened for CS were reviewed. CS was defined as a multidisciplinary team (MDT) consensus diagnosis. Univariate and multivariate binary logistic regressions were used to identify factors associated with CS, assessing their diagnostic performance, and integrating them into a diagnostic model., Results: Out of 354 patients (average age 51.5 years, 52.5% male), 18.4% were diagnosed with CS. In our cohort, male gender, a QRS duration > 120 ms, and nsVT on Holter monitoring were identified as significant markers associated with CS. Combining age, gender, AV-block or QRS > 120ms on ECG, and nsVT on Holter monitoring provided the highest diagnostic accuracy (AUC of 0.82). Cardiac biomarkers NT-proBNP and troponin T did not improve the diagnostic performance., Conclusion: In our cohort, male gender, a QRS duration > 120 ms, and nsVT on Holter monitoring were identified as significant markers associated with the presence of cardiac sarcoidosis. These clinical markers may aid in selecting sarcoidosis patients for screening with advanced cardiac imaging, potentially leading to earlier detection and management of the disease., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of interests We declare no competing interests.

Background: Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxaemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage (BAL), evaluation of antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), genetic testing and, eventually, lung biopsy. The management options are focused on removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis and lung transplantation. The presented diagnostic and management guidelines aim to provide guidance to physicians managing patients with PAP., Methods: A European Respiratory Society Task Force composed of clinicians, methodologists and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of evidence and strength of recommendations. The Task Force formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions and two narrative questions to develop specific evidence-based recommendations., Results: The Task Force developed recommendations for the five PICO questions. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis and lung transplantation. Also, the Task Force made recommendations regarding the use of GM-CSF antibody testing, diagnostic BAL and biopsy based on the narrative questions. In addition to the recommendations, the Task Force provided information on the hierarchy of diagnostic interventions and therapy., Conclusions: The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas the diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited., Competing Interests: Conflict of interest: C. McCarthy, F. Bonella, B.C. Trapnell and M. Griese report membership of a scientific advisory board of Savara Inc. B.C. Trapnell reports grants from the NHLBI (HL085453) and Savara, consultancy fees from Savara, and support for attending meetings from Savara. T. Wang reports grants from Savara, consultancy fees from Partner Therapeutics and Savara, payment or honoraria for lectures, presentations, manuscript writing or educational events from Partner Therapeutics and Savara, support for attending meetings from the PAP Foundation, participation on a data safety monitoring board or advisory board with Partner Therapeutics and Savara Inc., and a leadership role with the PAP Foundation (Clinical Director and Vice President). C. McCarthy reports grants from Health Research Board, Ireland, Enterprise Ireland and The LAM Foundation, consultancy fees from Theravance Inc., Savara Inc. and AI Therapeutics, support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Savara Inc. F. Bonella reports consultancy fees from Boehringer Ingelheim, Sanofi, BMS and Savara Inc., payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Sanofi, support for attending meetings from Boehringer Ingelheim, AstraZeneca, Atyr and Savara Pharma, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim, Sanofi and BMS. M. Fally reports leadership roles with the European Respiratory Society (Member of the Clinical Practice Guidelines Methodology Network and Secretary of Assembly 10, Group 1) and Danish Medical Journal (Associate Editor). A. Hadchouel reports patent issued (PCT/EP2022/064179). S. Jouneau reports the following financial (or non-financial) interests: PI for IMPALA and IMPALA-2 studies (Savara Inc.). R. Borie reports honoraria from Boehringer Ingelheim, Sanofi and Ferrer, support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Savara. I. Campo reports consultancy fees from Partner's Therapeutics, and participation on a data safety monitoring board or advisory board with Savara. E. Manali reports grants from Savara, consulting fees from Boehringer Ingelheim, CLS Behring and Hoffman-La Roche, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, CLS Behring and Hoffman-La Roche, support for attending meetings from Boehringer Ingelheim, CLS Behring, Hoffman-La Roche and Elpen, and a leadership role with the European Respiratory Society (Chair in ERS Task Force for Transition of chILD). H. Prosch reports grants from Boehringer Ingelheim, AstraZeneca, Siemens Healthineers, the Christian Doppler Research Association and EU Commission (EU4Health, Horizon Europe Health), consultancy fees from Boehringer Ingelheim and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, BMS, Boehringer Ingelheim, Bracco, Daiichi Sankyo, Janssen, MSD, Novartis, Roche, Sanofi, Siemens Healthineers and Takeda, support for attending meetings from Boehringer Ingelheim, participation on a data safety monitoring board or advisory board with Boehringer Ingelheim, and a leadership role with the European Society of Thoracic Imaging (Vice President). M. Veltkamp reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Chiesi, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim and Xentria. E. Bendstrup reports honoraria from Boehringer Ingelheim, AstraZeneca and Daichii Sankyo, support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim and Simbec-Orion. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Reducing the risk of high-grade primary graft dysfunction (PGD) is vital to achieve acceptable short- and long-term outcomes for recipients following lung transplantation. However, the utilization of injured lung allografts, which may confer a higher risk of PGD, must be considered due to the disparity between the increasing number of patients requiring lung transplantation and the limited donor pool. We describe a case in which highly marginal lung allografts were utilized with a good post-transplant outcome. Donor-recipient PGD risk compatibility was taken into consideration. Normothermic ex vivo lung perfusion (EVLP) was utilized to functionally assess the allografts. A second cold ischemia time following EVLP was avoided by converting the EVLP mode to a hypothermic oxygenated perfusion setup from which the lungs were transplanted directly. We attempted to mitigate lung ischemia-reperfusion injury in the recipient by employing cytokine adsorption both during the EVLP and intraoperatively during the implant procedure. In this case report, we describe our hypothermic oxygenated perfusion setup on EVLP for the first time. Furthermore, we describe the utilization of cytokine adsorption in two phases of the same transplant process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Braithwaite, Jennekens, Berg, de Heer, Ramjankhan, de Jong, Luc Charlier, Dessing, Veltkamp, Scheren, Ruigrok, Schönwetter, Buhre and van der Kaaij.)

Background and Aim: In sarcoidosis which is not threatening vital internal organs such as heart, central nervous system or lungs immunomodulatory treatment, such as hydroxychloroquine can be considered. Despite its common use, limited data are available regarding effectiveness and side effects as monotherapy in sarcoidosis. Recommendations on its usage are based on expert opinion as literature is scarce., Methods: This retrospective study examines real-world data about the indications, effectivity and side effects of hydroxychloroquine monotherapy in sarcoidosis patients with no damage to the vital internal organs. Successful treatment was defined as continuation after 24 weeks without step up therapy or worsening of symptoms., Results: Sixty patients were eligible for the study. Starting dose was 400mg/day, lowered to 200mg/day after 3 months in most patients. The predominant treatment indications were musculoskeletal 45 (75%) and cutaneous involvement 13 (22%). Thirty-three patients (55%) continued treatment after 24 weeks. Twenty-four patients (40%) mentioned side effects, mainly gastrointestinal, leading to treatment discontinuation in eleven patients (18%). No severe side effects were seen. Continuation after 24 weeks was significantly higher in patients with cutaneous involvement compared to other indications 85% vs 47% respectively (p =0.02)., Conclusions: Treatment with hydroxychloroquine monotherapy was satisfactory in 55% of patients, especially for cutaneous involvement. However, it poses considerable non-severe side-effects.

Purpose of Review: There is a clinical unmet need to improve treatment for patients with pulmonary sarcoidosis. Both retrospective and prospective drug trials are hampered by the fact that patients with sarcoidosis are characterized by a heterogeneous presentation and disease course. In this review, an overview is given of different drug trials in pulmonary sarcoidosis with an emphasis on different primary endpoints and the problems related to them., Recent Findings: In recent years, using significant input from patients with sarcoidosis, different task-forces/studies tried to develop a core set of most important outcomes to measure in future studies on treatment of sarcoidosis. Furthermore, at present, three major clinical trials are being conducted on new drugs for treatment of pulmonary sarcoidosis., Summary: Progress has been made to develop a core set of outcomes measures that can be used in making a combined primary endpoint in future drug trials in sarcoidosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Small fiber neuropathy is a common complication in patients with sarcoidosis and its prevalence is estimated at 40-86%. The underlying mechanism influences the presentation of small fiber neuropathy. For example, patients with metabolic diseases are often associated with a classic length-dependent small fiber neuropathy pattern, while patients with inflammatory diseases are more often present with a non-length-dependent small fiber neuropathy. Detailed phenotyping may be useful to improve diagnostic efficiency, as a clue to underlying mechanisms and as a precondition for personalized medicine. This study examined four phenotypes distinguishing between length-dependent and non-length-dependent presentation with a new subdivision for continuous and intermittent presentation. Forty-eight sarcoid patients with symptoms and at least two clinical signs of small fiber neuropathy and normal nerve conduction studies were classified as having probable small fiber neuropathy. A new small fiber neuropathy phenotyping questionnaire has been developed that allows patients to mark the anatomical locations of pain at three different levels: the skin, muscles, and joints. The location of symptoms was used to define length dependence, and two colors were used to distinguish continuous (red) from intermittent (blue) symptoms. In addition, skin biopsy, corneal confocal microscopy, Sudoscan and water immersion skin wrinkling were used to investigate a correlation between the four phenotypes, sensory function, nerve fiber density, and autonomic nerve function. Overall, 35% of patients with probable small fiber neuropathy showed length-dependent symptoms and 44% showed non-length-dependent symptoms while 21% suffered from non-neuropathic musculoskeletal pain. The distinction between intermittent and continuous symptoms showed significantly less continuous than intermittent non-length-dependent symptoms (odds ratio = 0.3, P = 0.01). Moreover, continuous length-dependent symptoms were the only phenotype that correlated with thermal threshold testing ( R = 0.3; P = 0.02) and the small fiber neuropathy screening list ( R = 0.3; P = 0.03). In addition, thermal threshold testing (TTT) also correlated with the small fiber neuropathy (SFN) screening list ( R = 0.3; P = 0.03). Other diagnostic methods showed no correlation with any of the four defined phenotypes. A novel finding is that TTT is only associated with continuous length-dependent pain, suggesting that TTT could result in more false negatives in patients with other pain phenotypes. Determining the pathophysiologic mechanisms could help develop new diagnostic methods. If patients suspected of SFN show symptoms without a length-dependent continuous presentation, the diagnosis should focus less on the diagnostic methods used., Competing Interests: Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement, etc.) that might pose a conflict of interest in connection with the submitted article., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking., Objective: In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy., Methods: Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment)., Results: Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032)., Conclusion: This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis., (© 2024. The Author(s).)

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

This article summarises a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the International Congress of the European Respiratory Society in 2023. Translational and clinical studies focused on the whole spectrum of ILDs, from (ultra)rare ILDs to sarcoidosis, ILDs associated with connective tissue disease and idiopathic pulmonary fibrosis. The main topics of the 2023 Congress presentations were improving the diagnostic process of ILDs, better prediction of disease course and investigation of novel treatment options., Competing Interests: Conflict of interest: L. Fabbri, J. Guiot and E. Bargagli have nothing to disclose. Conflict of interest: M. Vermant reports travel fees from Sanofi, outside the submitted work. Conflict of interest: E. Miądlikowska reports travel fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: D. Estrella reports travel fees from Sanofi and Roche/Genentech outside the submitted work. Conflict of interest: M.S. Wijsenbeek reports grants from Boehringer Ingelheim and Hoffmann la Roche, and fees from Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Galecto, Hoffman la Roche, Horizon Therapeutics, Kinevant Sciences, Molecure, Nerre Therapeutics, Novartis, PureTech Health, Respivant and CSL Behring, outside the submitted work, paid to her institution. Conflict of interest: W. Wuyts reports grants and fees from Boehringer Ingelheim, Hoffman la Roche, Galapagos and Sanofi, outside the submitted work, paid to his institution. Conflict of interest: A. Froidure reports grants and fees from Boehringer Ingelheim. Conflict of interest: P. Spagnolo reports grants from PPM Services, Roche and Boehringer Ingelheim, outside the submitted work, paid to his institution; and fees from PPM Services, Novartis, Pieris, Glycocore Pharma, Galapagos, Boehringer Ingelheim and Menarini outside the submitted work. Conflict of interest: M. Veltkamp reports fees from Boehringer Ingelheim and Chiesi outside the submitted work. Conflict of interest: M. Molina-Molina reports grants and fees from Boehringer Ingelheim, Roche, Chiesi and Ferrer, outside the submitted work. Conflict of interest: C. McCarthy reports grants and fees from Boehringer Ingelheim, Savara Inc., AI Therapeutics and Theravance Inc., outside the submitted work. Conflict of interest: K. Antoniou reports grants and fees from Boehringer Ingelheim, Hoffmann la Roche, GlaxoSmithKline, AstraZeneca, Chiesi and Menarini outside the submitted work. Conflict of interest: M. Kreuter reports grants and fees from Boehringer Ingelheim, Hoffman la Roche and Nichtraucherhelden/Sanero outside the submitted work. Conflict of interest: C.C. Moor reports grants and fees from Boehringer Ingelheim, Hoffmann la Roche, AstraZeneca and Daiichi Sankyo, outside the submitted work, paid to her institution., (Copyright ©The authors 2024.)

At present, no biomarker exists which is truly specific for sarcoidosis and the ones available have modest sensitivity and specificity. The clinical context should dictate the choice of biomarker(s) used to address different clinical questions such as diagnosis, monitoring disease activity or monitoring response to treatment. In the future, in addition to known serum biomarkers, it seems fruitful to further explore a possible role of imaging, exhaled air and even biopsy-related biomarkers in sarcoidosis to guide clinical management., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: No guidelines are available on the preferred method for analyzing corneal confocal microscopy (CCM) data. Manual, semiautomatic, and automatic analyzes are all currently in use. The purpose of the present study was threefold. First, we aimed to investigate the different methods for CCM analysis in patients with and without small fiber neuropathy (SFN). Second, to determine the correlation of different methods for measuring corneal nerve fiber length (CNFL) and nerve fiber area (NFA). Finally, we investigated the added value of automatic NFA analysis., Methods: We included 20 healthy controls and 80 patients with sarcoidosis, 31 with established SFN and 49 without SFN. The CNFL was measured using CCMetrics, ACCMetrics, and NeuronJ. NFA was measured with NFA FIJI and ACCMetrics NFA., Results: CNFL and NFA could not distinguish sarcoidosis with and without SFN or healthy controls. CCMetrics, NeuronJ, and ACCMetrics CNFL highly correlated. Also, NFA FIJI and ACCMetrics NFA highly correlated. Reproducing a nonlinear formula between CNFL and NFA confirmed the quadratic relation between NFA FIJI and ACCMetrics CNFL. CCMetrics and NeuronJ instead showed a square root relationship and seem to be less comparable owing to differences between automatic and manual techniques., Conclusions: ACCMetrics can be used for fully automatic analysis of CCM images to optimize efficiency. However, CNFL and NFA do not seem to have a discriminatory value for SFN in sarcoidosis. Further research is needed to determine the added value and normative values of NFA in CCM analysis., Translational Relevance: Our study improves the knowledge about CCM software and pathophysiology of SFN.

Introduction: Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG (n=1-5) resulting in enhanced cellular retention. In this study we address the question whether different MTXPG (n) concentrations in red blood cells (RBC) of patients with sarcoidosis after 3 months of MTX therapy correlate with response to treatment., Methods: We retrospectively included patients with sarcoidosis that had started on MTX therapy and from whom blood samples and FDG-PET/CT were available 3 and 6-12 months after MTX initiation, respectively. FDG-uptake was measured by SUVmax in the heart, lungs and thoracic lymph nodes. Changes in SUVmax was used to determine anti-inflammatory response after 6-12 months of MTX therapy. MTXPG (n) concentrations were measured from whole blood RBC using an LC-MS/MS method. Pearson correlation coefficients were calculated to evaluate the relationship between changes in the SUVmax and MTXPG (n) concentrations., Results: We included 42 sarcoidosis patients treated with MTX (15 mg/week); 31 with cardiac sarcoidosis and 11 with pulmonary sarcoidosis. In MTXPG 3 and MTXPG 4 a significant negative relation between the absolute changes in SUVmax and MTXPG (n) was found r = - 0.312 (n = 42, p = 0.047) for MTXPG 3 and r = - 0.336 (n = 42, p = 0.031 for MTXPG 4 ). The other MTXPG (n) did not correlate to changes in SUVmax., Conclusion: These results suggest a relation between MTXPG (n) concentrations and the anti-inflammatory effect in patients with sarcoidosis. Further prospective validation is warranted, but if measuring MTXPG concentrations could predict treatment effect of MTX this would be a step in the direction of personalized medicine., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Several recent studies of diagnosing small fiber neuropathy (SFN) have shown a lack of uniformity in thermal threshold testing (TTT) or quantitative sensory testing (QST) which makes it a challenge to compare the data. It is known that the chance of finding an abnormality increases with increasing number of measurements., Objectives: With this study, we first wanted to investigate whether TTT could benefit from a new approach focusing on the balance between the number of measurements, depending on the selection of parameters and measuring sites, and on number of abnormalities (NOAs). Second, we wanted to address the role of the method of levels (MLe) in possible desensitization during TTT measurements., Methods: One hundred seventeen participants were included (48 patients with sarcoidosis with probable SFN, 49 without SFN, and 20 healthy controls). Thermal threshold testing measurements and Small Fiber Neuropathy Screening List (SFNSL) questionnaire were used to assess SFN., Results: A combination of measuring all thermal threshold parameters at both feet except for MLe showed the best diagnostic performance. Increasing TTT NOAs correlates with the severity of SFN. Adding the SFNSL questionnaire further improves diagnostic performance., Discussion: Looking at TTT NOAs in all TTT parameters except for MLe at both feet should be considered as a new approach to improve the consistency and balance between the selection of TTT parameters, measuring sites, and definition of "abnormal QST." Moreover, the SFNSL questionnaire is a valuable tool to quantify SFN symptoms and could improve SFN diagnosis., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

The unknown etiology of sarcoidosis, along with the variability in organ involvement and disease course, complicates the effective treatment of this disease. Based on recent studies, the cellular inflammatory pathways involved in granuloma formation are of interest regarding possible new treatment options, such as the mechanistic (formerly mammalian) target of rapamycin complex 1 (mTORC1) pathway, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome pathway. The aim of this study was to explore the potential coexpression of these three inflammatory pathways in patients with sarcoidosis and see whether possible differences were related to disease outcome. The tissue of 60 patients with sarcoidosis was used to determine the activity of these three signaling pathways using immunohistochemistry. The activation of NLRP3 was present in 85% of all patients, and the activation of mTORC1 and JAK/STAT was present in 49% and 50% of patients, respectively. Furthermore, the presence of NLRP3 activation at diagnosis was associated with a chronic disease course of sarcoidosis. Our finding of different new conceptual inflammatory tissue phenotypes in sarcoidosis could possibly guide future treatment studies using the available inhibitors of either NLRP3, JAK-STAT, and mTORC1 inhibitors in a more personalized medicine approach.

Purpose: Pirfenidone and nintedanib unequivocally inhibit FVC decline, but have been inconsistently linked to reduced mortality in phase III studies. On the contrary, real-world data show a survival benefit of antifibrotic drugs. However, it is unknown what this benefit is across different Gender, Age, and Physiology (GAP) stages., Research Questions: Is there a difference in transplant-free (TPF) survival of IPF patients receiving antifibrotic drugs (IPF AF ) compared with an untreated cohort (IPF non-AF )? Is this different for patients with GAP stage I, II, or III., Methods: This is a single-center observational cohort study using prospectively included patients diagnosed with IPF between 2008-2018. Primary outcomes were TPF survival difference and 1-, 2-, and 3-year cumulative mortality for IPF AF and IPF non-AF . This was repeated after stratification for GAP stage., Results: In total, 457 patients were included. The median transplant-free survival was 3.4 years in IPF AF (n = 313) and 2.2 years in IPF non-AF (n = 144, p = 0.005). For GAP stage II, a median survival of 3.1 and 1.7 years was noted for IPF AF (n = 143) and IPF non-AF (n = 59, p < 0.001), respectively. A significantly lower 1-, 2-, and 3- year cumulative mortality was found for IPF AF with GAP stage II (1 yr: 7.0% vs 35.6%, 2 yr: 26.6% vs 55.9%, and 3 yr: 46.9% vs 69.5%). The 1-year cumulative mortality of IPF AF with GAP III was also significantly lower (19.0% vs 65.0%)., Conclusion: This large real-world study showed a survival benefit in IPF AF compared with IPF non-AF . This especially holds true for patients with GAP stage II and III., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients., Methods and Results: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups., Conclusions: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

This article contains a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the hybrid European Respiratory Society International Congress 2022. Early Career Members of Assembly 12 summarise recent advances in translational and clinical research in idiopathic interstitial pneumonias, ILDs of known origin, sarcoidosis and other granulomatous diseases, and rare ILDs. Many studies focused on evaluation of diagnostic and prognostic (bio)markers, and novel pharmacological and nonpharmacological treatment options for different ILDs. In addition, new insights in clinical, physiological and radiological features of various rare ILDs were presented., Competing Interests: Conflict of interest: K.M. Antoniou has received consulting fees from BI, GSK and Roche, outside the submitted work; payment or honoraria from BI, Roche, Chiesi, Menarini, GSK and AstraZeneca, outside the submitted work. C. McCarthy has received grants or contracts from Health Research Board, Ireland, Enterprise Ireland and The LAM Foundation, outside the submitted work; consulting fees from Savara Inc., AI Therapeutics and Theravance Inc., outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Savara Inc., outside the submitted work; and is a Breathe (published by ERS) editorial board member. M. Veltkamp has received consulting fees from Boehringer Ingelheim and Chiesi, outside the submitted work; payment or honoraria from Boehringer Ingelheim, outside the submitted work; participation on a data safety monitoring or advisory board for COLD study (Kalverda and Annema) on cryobiopsy in ILD, outside the submitted work. A. Froidure has received consulting fees from Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work; payment or honoraria from Boehringer Ingelheim, outside the submitted work; and support for attending meetings and/or travel from Sanofi, outside the submitted work. M. Molina-Molina received grants or contracts from Boehringer Ingelheim, Roche, outside the submitted work; consulting fees from Ferrer, Boehringer Ingelheim, Roche, outside the submitted work; payment or honoraria from Chiesi, Roche, Boehringer Ingelheim outside the submitted work; and support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work. W.A. Wuyts has received grants or contracts from Roche, Boehringer Ingelheim and Galapagos, outside the submitted work; consulting fees from Roche, Boehringer Ingelheim, Galapagos and Sanofi, outside the submitted work; participation on a data safety monitoring or advisory board for Roche, Boehringer Ingelheim and Sanofi, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: working group Belgian respiratory society (unpaid) and ERS group 12.1 (unpaid), outside the submitted work. D.W. Loth has received payment or honoraria from Boehringer Ingelheim B.V., outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim B.V., outside the submitted work. E. Khurtsidze has received grants or contracts from Erasmus, outside the submitted work. M. Kreuter has received grants or contracts from Boehringer and Roche, outside the submitted work; consulting fees from Boehringer and Roche, outside the submitted work; payment or honoraria from Boehringer, Novartis, and Roche, outside the submitted work. P. Spagnolo has received grants or contracts from Roche, Boehringer Ingelheim and PPM Services, outside the submitted work; consulting fees from PPM Services, Chiesi, Galapagos, Behring, Santhera Pharmaceuticals and Novartis, outside the submitted work; payment or honoraria from Chiesi, Boehringer Ingelheim, outside the submitted work; participation on a data safety monitoring or advisory board for Galapagos, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group for ERS group 12.03 (Group chair, unpaid), outside the submitted work. P.P. Diep received payment or honoraria from Boehringer Ingelheim Norway, honoraria for presentations, outside the submitted work; support for attending the Nordic ILD-congress in Stockholm 2021, outside the submitted work. C.C. Moor has received grants or contracts from Boehringer Ingelheim, AstraZeneca and Daiichi-Sankyo, outside the submitted work; payment or honoraria from Boehringer Ingelheim, Hoffman–la Roche, outside the submitted work; ERS Early Career Member Committee, outside the submitted work. M.S. Wijsenbeek has received grants or contracts from Boehringer Ingelheim; Hoffman la Roche; The Netherlands Organisation for Health Research and Development; The Dutch Lung Foundation; The Dutch Pulmonary Fibrosis, outside the submitted work; consulting fees from Bristol Myers Squibb, Boehringer Ingelheim, Galapagos, Galecto, Hoffman la Roche, Horizon therapeutics, Kinevant Sciences, Molecure, Nerre Therapeutics, Novartis, PureTech Health, and Respivant, outside the submitted work; payment or honoraria from Boehringer Ingelheim, CSL Behring, Hoffman la Roche and Novartis, outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim and Hoffman la Roche Galapagos, outside the submitted work; participation on a data safety monitoring or advisory board for Savara, Galapagos, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group for Chair of the Idiopathic Interstitial Pneumonia group of the European Respiratory Society; member of the board of the Netherlands Respiratory Society; member of the scientific advisory board of the European Idiopathic Pulmonary Fibrosis and Related Disorders Federation; Chair of the educational committee of the European Reference Network for Rare Lung Diseases; advisory board of the Dutch Lungfibrosis and Sarcoidosis patient associations (unpaid), outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP)., Methods: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change., Results: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045)., Interpretation: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression., Competing Interests: Conflict of interest: J. Jacob reports fees from Boehringer Ingelheim, Roche, NHSX, Takeda and GlaxoSmithKline unrelated to the submitted work. J. Jacob was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z and the NIHR Biomedical Research Centre at University College London. S.M. Janes reports fees from AstraZeneca, Bard1 Bioscience, Achilles Therapeutics and Janssen unrelated to the submitted work. S.M. Janes received assistance for travel to meetings from AstraZeneca to American Thoracic Conference 2018 and from Takeda to World Conference Lung Cancer 2019, and is the Investigator Lead on grants from GRAIL Inc, GlaxoSmithKline plc and Owlstone. A.U. Wells reports personal fees and nonfinancial support from Boehringer Ingelheim, Bayer and Roche Pharmaceuticals; and personal fees from Blade, outside of the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Sarcoidosis-associated fatigue is highly prevalent and is often reported as the most burdensome symptom of sarcoidosis. Management of fatigue is challenging, and evidence-based therapies are lacking. In this TIRED trial, we aimed to assess the effects of a 12-week online mindfulness-based cognitive therapy (eMBCT) on fatigue., Methods: This study was a prospective, open-label, multicentre randomised controlled trial, conducted at three centres in the Netherlands. Eligible patients were 18 years or older, had stable sarcoidosis, and a score of more than 21 points on the Fatigue Assessment Scale (FAS). Patients were randomised into either the eMBCT or the control group. Participants completed patient-reported outcome measures at baseline, after intervention (T1), and 12 weeks after completion of eMBCT (T2). The primary outcome was the change in FAS score at T1 in the eMBCT group compared with the control group, assessed with the independent students't test in all patients who started the study. Secondary outcomes included within-group difference in FAS score at T1 and T2, between-group difference in FAS score at T2, and changes in the Hospital Anxiety and Depression Scale, the Freiburg Mindfulness Inventory-Short Form, and the Kings Sarcoidosis Questionnaire. The study was registered at the Netherlands Trial Register, NL7816., Findings: Between June 5, 2019, and Oct 28, 2021, 99 patients were randomly assigned to the eMBCT (n=52) or the control (n=47) groups. Six patients withdrew consent after psychological screening before the start of eMBCT. Baseline FAS score was similar in both groups (34·57 [SD 6·07] for 46 patients in the eMBCT group and 35·51 [4·65] for 47 patients in the control group). Mean change in FAS score at T1 was -4·53 (SD 5·77; p<0·0001) in the eMBCT group and -1·28 (3·80; p=0·026) in the control group (between-group difference 3·26 [95% CI 1·18 to 5·33; p=0·0025]). Furthermore, the eMBCT group had a significant improvement in anxiety (mean between-group difference 1·69, 95% CI 0·22-3·16; p=0·025), depressive symptoms (1·52, 0·08-2·95; p=0·039), mindfulness (3·1, 0·70-5·49; p=0·022), and general health status (6·28, 2·51-10·06; p=0·002) at T1, compared with the control group., Interpretation: 12 week eMBCT improves fatigue, anxiety, depression, mindfulness, and health status in patients with sarcoidosis-associated fatigue., Funding: Dutch Sarcoidosis Patient Association (Sarcoidose.nl)., Translation: For the Dutch translation of the summary see Supplementary Materials section., Competing Interests: Declaration of interests MLvdL works at the Helen Dowling Institute but has no financial interest. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aim: Small fiber neuropathy (SFN) may present as complication in sarcoidosis.(1) SFN can potentially result into a large range of symptoms with a high impact on quality of life.(2) Although treatment of the underlying disease of SFN is paramount, little research has been performed to investigate SFN improvement as consequence of sarcoidosis treatment. This retrospective study investigates whether there is an association between the anti-inflammatory effects of infliximab and SFN-symptoms Methods: The Small Fiber Neuropathy Screening List (SFNSL) was used to measure changes in SFN symptoms during infliximab treatment. Maximal standardized uptake value (SUVmax) from Fluordeoxyglucose Positron Emission Tomography (FDG-PET) was used as a measure for inflammatory activity., Results: 36 sarcoidosis patients were eligible for analysis. SFNSL-score showed a mean decrease of -1,9 points (p = 0.446). SUVmax did improve with a mean of -3.7 (p<0.001). No correlation between a decrease of SUVmax and SFNSL screening list could be found (p=0.610)., Conclusions: Our data reveal no association between anti-inflammatory effect of infliximab and SFN-related symptoms in patients with sarcoidosis, which contradicts previous case-reports and case-series.(3-6) Given the major negative impact of SFN-related symptoms on the quality of life in patients with sarcoidosis, it is necessary that the possible beneficial effect of anti-inflammatory therapy will be further addressed in future prospective studies.1.

Cutibacterium acnes ( C. acnes , formerly Propionibacterium acnes ) is considered to be a non-pathogenic resident of the human skin, as well as mucosal surfaces. However, it also has been demonstrated that C. acnes plays a pathogenic role in diseases such as acne vulgaris or implant infections after orthopedic surgery. Besides a role in infectious disease, this bacterium also seems to harbor immunomodulatory effects demonstrated by studies using C. acnes to enhance anti-tumor activity in various cancers or vaccination response. Sarcoidosis is a systemic inflammatory disorder of unknown causes. Cultures of C. acnes in biopsy samples of sarcoidosis patients, its presence in BAL fluid, tissue samples as well as antibodies against this bacterium found in serum of patients with sarcoidosis suggest an etiological role in this disease. In this review we address the antigenic as well as immunomodulatory potential of C. acnes with a focus on sarcoidosis. Furthermore, a potential role for antibiotic treatment in patients with sarcoidosis will be explored.

Background: Cardiac sarcoidosis (CS) is associated with an increased risk for sudden cardiac death. An implantable cardiac defibrillator (ICD) is recommended in a subgroup of CS patients. However, the recommendations for primary prevention differ between guidelines. The purpose of the study was to evaluate the efficacy and safety of ICDs in CS and to identify predictors of appropriate therapy., Methods: A retrospective cohort study was performed in CS patients with an ICD implantation between 2010 and 2019. Primary outcome was appropriate ICD therapy. Independent predictors were calculated using Cox proportional hazard analysis., Results: 105 patients were included. An ICD was implanted for primary prevention in 79%. During a median follow-up of 2.8 years, 34 patients (32.4%) received appropriate ICD therapy of whom 24 (22.9%) received an appropriate shock. Three patients (2.9%) received an inappropriate shock due to atrial fibrillation. Independent predictors of appropriate therapy included prior ventricular arrhythmias (hazard ratio [HR]: 10.5 [95% confidence interval (CI): 5.0-21.9]) and right ventricular late gadolinium enhancement (LGE) (HR: 3.6 [95% CI: 1.7-7.6]). Within the primary prevention group, right ventricular LGE (HR: 5.7 [95% CI: 1.6-20.7]) was the only independent predictor of appropriate therapy. Left ventricular ejection fraction did not differ between patients with and without appropriate therapy (44.4% vs. 45.6%, p = .70)., Conclusion: In CS patients with an ICD, a high rate of appropriate therapy was observed and a low rate of inappropriate shocks. Prior ventricular arrhythmias and right ventricular LGE were independent predictors of appropriate therapy., (© 2022 Wiley Periodicals LLC.)

Background: Pirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than IPF. However, the safety and effectiveness of pirfenidone in asbestosis patients remain unclear. In this study, we aimed to investigate the safety, tolerability and efficacy of pirfenidone in asbestosis patients with a progressive phenotype., Methods: This was a multicenter prospective study in asbestosis patients with progressive lung function decline. After a 12-week observational period, patients were treated with pirfenidone 801 mg three times a day. Symptoms and adverse events were evaluated weekly and patients completed online patient-reported outcomes measures. At baseline, start of therapy, 12 and 24 weeks, in hospital measurement of lung function and a 6 min walking test were performed. Additionally, patients performed daily home spirometry measurements., Results: In total, 10 patients were included of whom 6 patients (66.7%) experienced any adverse events during the study period. Most frequently reported adverse events were fatigue, rash, anorexia and cough, which mostly occurred intermittently and were reported as not very bothersome. No significant changes in hospital pulmonary function (forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), 6 min walking test or patient-reported outcomes measures before and after start of pirfenidone were found. Home spirometry demonstrated a FVC decline in 12 weeks before start of pirfenidone, while FVC did not decline during the 24 week treatment phase, but this difference was not statistically significant., Conclusions: Treatment with pirfenidone in asbestosis has an acceptable safety and tolerability profile and home spirometry data suggest this antifibrotic treatment might attenuate FVC decline in progressive asbestosis. Trial registration MEC-2018-1392; EudraCT number: 2018-001781-41., (© 2022. The Author(s).)