Background/Objectives: A significant number of patients experience prolonged symptoms following COVID-19 in particular cases of fatigue. Yet, pathomechanisms of COVID-19-related fatigue remain unclear. Methods: This study investigated patients after confirmed SARS-CoV-2 infection (PC) with relevant fatigue according to the Fatigue Assessment Scale (≥22 points) to rule out malnutrition as a driving factor for fatigue and to evaluate daily activity and sleep characteristics. Dietary behavior was recorded through food diaries and physical activity by self-reported (questionnaires) and objective (activity tracker) outcomes. Data were collected over a 7-day period and compared with a healthy control group (HC). A subgroup analysis of patients with fatigue and severe fatigue, as well as a sex-specific analysis, were included. Results: No significant differences in dietary intake were observed, but an indication toward a healthier Mediterranean diet in PC patients with a median Mediterranean Diet Score of 4 (IQR 3, 5) in HC vs. 5 (IQR 3, 6) in PC (p = 0.24). There were also no differences in physical activity, either by objective or subjective measures. However, the median sleep duration was 49 min longer in PC patients (p = 0.003). Conclusions: In conclusion, malnutrition did not significantly contribute to fatigue, yet patients with COVID-19-related fatigue showed increased sleep duration. As sleep characteristics play a crucial role in mental and physical wellbeing, the association of sleep, physical activity, and fatigue should be evaluated in further studies.

Septic aneurysms of the pulmonary artery are rare conditions, with few cases having been reported worldwide. They are assumed to result from septic emboli that cause a local inflammatory reaction of the arterial wall, ultimately leading to degenerative changes. We report the case of a 63-year-old female patient presenting with Klebsiella pneumoniae urosepsis and first diagnosis of diabetes mellitus, who developed a life-threatening infectious pulmonary artery aneurysm secondary to bacteremia with Klebsiella pneumoniae. The patient required a lobectomy due to pulmonary hemorrhage. We review the clinical hallmarks of Klebsiella pneumoniae related septic pulmonary embolic disease and summarize currently known risk factors for the development of infectious aneurysmatic disease including diabetes mellitus and other states of immunosuppression. The featured case aims to increase the awareness for this seldom but life-threatening complication of infectious diseases such as Klebsiella pneumoniae urosepsis.

Erj;64/suppl_68/OA953/F1 F1 F1 Background/Objectives: This study aims to explore the immune landscape of pulmonary sarcoidosis at single-cell level to enhance our understanding of the development, role and impact of TH17.1 inflammation, repeatedly observed in BAL and affected tissues. Methods: We examined BAL fluid from 16 sarcoidosis patients and 10 control individuals using single-cell RNA sequencing (scRNAseq), ELISA and flow cytometry with and without prior stimulation. Results: Transcriptional profiling of approximately 85,000 native BAL cells revealed a notable expansion of myeloid cells expressing CXCL10 and CCL2 in sarcoidosis patients together with increased GM-CSF levels. At the T-cell level, a moderate TH17.1 signature was present in native cells, with further inducibility upon stimulation. In contrast, TH cells in the control group displayed only an inducible TH1 signature. Flow cytometry validation analyses demonstrated an increase in TH17.1 cell populations in the sarcoidosis group upon stimulation. Analysis of potential ligand-receptor pairs between myeloid and TH17.1 cells suggested an enhanced interaction through multiple upregulated chemokine signaling pathways. Discussion: Our findings confirm the presence of a proinflammatory TH17.1 cell population in the BAL of sarcoidosis patients, while emergence of CXCL10+ macrophages may contribute to generation and activation of TH17.1 cells.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix, which can be measured by collagen synthesis neoepitopes. We hypothesized that the trajectory of neoepitopes following antifibrotics predicts outcomes. Methods: Two cohorts of 203 IPF patients from two university hospitals were recruited. Serum at baseline and following 3-6 months of nintedanib or pirfenidone were measured for MMP degraded type 3 collagen (C3M), -type 6 collagen (C6M), -C-reactive protein (CRPM) and type 3 collagen (pro-C6) via ELISA. Association of neoepitopes with pulmonary function tests and progression-free-survival (PFS) was analyzed. Results: Age was 71 years and 20.7% were female with a median follow-up of 1.9 years. 50% received nintedanib, 35% pirfenidone and 15% did not receive antifibrotics. In the pooled cohort, patients with increasing CRPM and pro-C6 levels had worse PFS compared with decreasing levels (adj. HR 1.63, p=0.011 and adj. HR 1.7, p=0.012). In both cohorts, these effects were driven by nintedanib, where increasing levels were associated with poor PFS while not by pirfenidone. We then conducted a competing risk regression analysis with FVC or DLCO decline as the outcome and death or transplant as competing events, demonstrating a strong association between increasing CRPM levels and progression with nintedanib treatment (SHR 11.8; p=0.001) but not with pirfenidone (HR 0.32; p=0.057). Increase of CRPM was also inversely correlated with time to progression (R=-0.32; p=0.033) with nintedanib. Conclusion: In IPF, increase of CRPM was associated with disease progression with nintedanib but not pirfenidone.

Rationale: Sarcoidosis is a granulomatous disease of unknown cause that may occur across multiple organs. While granulomas share a conserved histological architecture, their spatial cellular organization and organ-specific features remain incompletely understood. Methods: Sarcoidosis specimens containing granulomas were collected from three centers (Hannover n=82, Aachen n=39, Paris n=7; total n=128), including lung, skin, lymph node, liver, kidney, heart, and bone marrow. 10x Genomics Visium HD spatial 2µm bins were converted into single-cell–resolved expression profiles. A ring-to-core distance metric was computed to capture spatial transcriptional gradients. Multinucleated giant cells were segmented manually. Results: Spatial single-cell profiling revealed pronounced intra-granulomatous myeloid heterogeneity with distinct macrophage and monocyte niches. SPP1+ monocyte-derived macrophages represented a conserved population present across all organs. Stromal compartments contained inflammatory fibroblasts localized to the granuloma periphery. Multinucleated giant cells showed a specialized macrophage program enriched for lysosomal lipid handling and mitochondrial stress responses. Conclusions: This multi-organ spatial single-cell atlas defines a conserved cellular blueprint of sarcoidosis granulomas with a ring-to-core myeloid differentiation axis and an inflammatory fibroblast boundary niche, providing a foundation for mechanistic insight and targeted therapeutic strategies. erj;68/suppl_70/OA3424/F1 F1 F1

Das Spektrum pulmonaler Blutungen reicht von der Erstdiagnose eines Malignoms bis hin zur Manifestation einer lebensbedrohlichen, rasch voranschreitenden Autoimmunerkrankung. Dabei ist ein rasches, geordnetes Handeln geboten, um einen potenziell fatalen Ausgang abzuwenden. Dieser Artikel illustriert anhand eines Fallbeispiels die differenzialdiagnostischen und therapeutischen Überlegungen bei Patient*innen mit einem akuten pulmonalen Blutungsgeschehen aus Sicht der Pneumolog*innen. Hemoptysis resembles a clinical emergency and necessitates a fast and well-coordinated diagnostic and therapeutic approach. While up to 50% of the underlying causes remain unidentified, the majority of cases in the western world can be attributed to respiratory infections and pulmonary neoplasm. While 10% of the patients present with massive, life-threatening hemoptysis, which require a timely airway protection in order to secure a sustained pulmonary gas-exchange, the vast majority presents with non-critical pulmonary bleeding events. Most critical pulmonary bleeding events arise from the bronchial circulation. An early chest imaging is key for identifying the bleeding cause and localization. While chest x-rays are widely implemented in the clinical work-flow and rapidly applicable, computed tomography and computed tomography angiography exhibit the highest diagnostic yield. Bronchoscopy can add diagnostic information especially in pathologies of the central airways, while offering multiple therapeutic options to maintain pulmonary gas exchange. The initial therapeutic regimen comprises early supportive care, but treatment of the underlying etiology is of prognostic relevance and avoids recurrent bleeding events. Bronchial arterial embolization usually is the therapy of choice in patients with massive hemoptysis, while definitive surgery is reserved for patients with refractory bleeding and complex pathologies. Article published online: 26 June 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany