Long-term outcomes in five patients with autoimmune pulmonary alveolar proteinosis treated with molgramostim inhalation solution.

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.

Holter Monitoring and Cardiac Biomarkers in Screening for Cardiac Sarcoidosis.

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.

Navigating sarcoidosis: Recognizing, managing, and supporting patients in primary care.

Background: Sarcoidosis is a chronic multisystem inflammatory disease of unknown aetiology, characterised by noncaseating granulomas and a variable clinical presentation. Despite its global distribution, sarcoidosis is relatively rare, with the highest prevalence in northern Europe. This poses challenges for primary care physicians due to its broad spectrum of symptoms, from organ-specific manifestations to general complaints like fatigue and concentration difficulties.

New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy.

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.

Clinical trials in pulmonary sarcoidosis; what is needed, what is happening and what is next?

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.

Vitamin K: a potential missing link in critical illness-a scoping review.

Background: Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach.

Is a Vitamin K Epoxide Reductase Complex Subunit 1 () Polymorphism a Risk Factor for Nephrolithiasis in Sarcoidosis?

Sarcoidosis is a systemic inflammatory disorder characterized by granuloma formation in various organs. It has been associated with nephrolithiasis. The vitamin K epoxide reductase complex subunit 1 () gene, which plays a crucial role in vitamin K metabolism, has been implicated in the activation of proteins associated with calcification, including in the forming of nephrolithiasis.

ERS International Congress 2023: highlights from the Interstitial Lung Diseases Assembly.

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.

Drug-Gene Risk Stratification in Patients with Suspected Drug-Induced Interstitial Lung Disease.

Background: Pulmonary toxicity has been associated with drug use. This is often not recognized in clinical practice, and underestimated.

Objective: We aimed to establish whether polymorphisms in certain genes corresponding with a metabolic pathway of drug(s) used are associated with pulmonary toxicity in patients with suspected drug-induced interstitial lung disease (DI-ILD).

A new variant in the gene: diverse clinical phenotypes and expression in the lung.

Introduction: Pulmonary fibrosis is a severe disease which can be familial. A genetic cause can only be found in ∼40% of families. Searching for shared novel genetic variants may aid the discovery of new genetic causes of disease.

Neurosarcoidosis and Neurologic Complications of Sarcoidosis Treatment.

Sarcoidosis is an immune-mediated multisystem granulomatous disorder. Neurosarcoidosis (NS) accounts for 5% to 35% of cases. The diagnostic evaluation of NS can be a clinical challenge.

Biomarkers in Sarcoidosis: Beginning of a New Era?

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.

New Insights via RNA Profiling of Formalin-Fixed Paraffin-Embedded Lung Tissue of Pulmonary Fibrosis Patients.

In sporadic idiopathic pulmonary fibrosis (sIPF) and pulmonary fibrosis caused by a mutation in telomere (TRG-PF) or surfactant related genes (SRG-PF), there are a number of aberrant cellular processes known that can lead to fibrogenesis. We investigated whether RNA expression of genes involved in these processes differed between sIPF, TRG-PF, and SRG-PF and whether expression levels were associated with survival. RNA expression of 28 genes was measured in lung biopsies of 26 sIPF, 17 TRG-PF, and 6 SRG-PF patients.

Fully Automatic, Semiautomatic, and Manual Corneal Nerve Fiber Analysis in Patients With Sarcoidosis.

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.

Methotrexate Polyglutamate Concentrations as a Possible Predictive Marker for Effectiveness of Methotrexate Therapy in Patients with Sarcoidosis: A Pilot Study.

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 resulting in enhanced cellular retention.

Establishing a Diagnosis of Pulmonary Sarcoidosis.

Pulmonary sarcoidosis is the most prevalent manifestation of sarcoidosis and the commonest diagnosis in clinics for ILD. Due to the lack of a simple and reliable test, making the diagnosis is often challenging. There are three criteria that must always be considered: (1) compatible clinical presentation; (2) evidence of granuloma formation (usually non-caseating); and (3) exclusion of alternative causes of granulomatous disease.

Thermal threshold testing: call for a balance between the number of measurements and abnormalities in the diagnosis of sarcoidosis-associated small fiber neuropathy.

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).

Simultaneous Assessment of mTORC1, JAK/STAT, and NLRP3 Inflammasome Activation Pathways in Patients with Sarcoidosis.

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.

Sarcoidosis and frailty: recognizing factors that foster holistic resilience.

Purpose Of Review: Sarcoidosis is a multiorgan system disease exerting significant impact on biophysical, social, psychological and emotional well-being. Mortality and disability correlate to accessible, timely, expert care for sarcoidosis and its related complications. Across health conditions, positive healthcare interactions and interventions can rehabilitate unfavourable factors tied to concepts of ' frailty' .