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Purpose: The role of lung biopsy for evaluation of persistent chest radiographic abnormalities including secondary organizing pneumonia (OP) in COVID-19 remains uncertain. This study aimed to evaluate the diagnostic value of trans-bronchial forceps biopsy (TBFB) in patients with persistent lung abnormalities on thoracic computed tomography (CT) scan following SARS-CoV-2 infection with particular focus on cases with OP and immunocompromised (IC) patients., Methods: Descriptive retrospective single center analysis of all TBFB performed for diffuse lung parenchymal changes after COVID-19 03-2020 to 06-2023., Results: Twenty seven consecutive TBFB including 23 in IC patients resulted in 100% samples with alveolar tissue showing a high frequency of 12/27 (44%) histological pattern of OP. Steroids were used in 21/27 patients (78%) including 11/12 (92%) with OP. Clinical outcome at discharge was favorable in 89% (92% with OP)., Conclusion: TBFB contributes to the diagnosis of diffuse parenchymal lung abnormalities in the context of COVID-19 including a frequent OP pattern particularly in IC patients. Larger studies are necessary to confirm our data and elucidate on the optimal steroid treatment modality., Trial Registration: Clinical trial number: not applicable. The study was approved by the Ethics Committee of the University Medicine Carl Gustav Carus, TU Dresden (BO-EK-309072023). Waiver of informed consent was granted because of the retrospective nature of the study., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of the University Medicine Carl Gustav Carus, TU Dresden (BO-EK-309072023). Waiver of informed consent was granted because of the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years., Methods: Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4. These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes' discovery., Results: A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH., Conclusions: Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes., (© 2022. The Author(s).)

Background: Inborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans., Objective: We sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency., Methods: We assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells., Results: SOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients., Conclusions: SOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients., 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., (Copyright © 2021 Körholz, Gabrielyan, Sowerby, Boschann, Chen, Paul, Brandt, Kleymann, Kolditz, Toepfner, Knöfler, Jacobsen, Wolf, Conrad, Röber, Lee-Kirsch, Smith, Mundlos, Berner, Dalpke, Schuetz and Rae.)

Background: Although combination therapy is the gold standard for patients with pulmonary arterial hypertension (PAH), some of these patients are still being treated with monotherapy., Methods: We conducted a retrospective analysis at four German PH centres to describe the prevalence and characteristics of patients receiving monotherapy., Results: We identified 131 incident PAH patients, with a mean age of 64 ± 13.8 years and a varying prevalence of comorbidities, cardiovascular risk factors and targeted therapy. As in other studies, the extent of prescribed PAH therapy varied with age and coexisting diseases, and younger, so-called "typical" PAH patients were more commonly treated early with combination therapy (48% at 4-8 months). In contrast, patients with multiple comorbidities or cardiovascular risk factors were more often treated with monotherapy (69% at 4-8 months). Survival at 12 months was not significantly associated with the number of PAH drugs used (single, dual, triple therapy) and was not different between "atypical" and "typical" PAH patients (89% vs. 85%)., Conclusion: Although "atypical" PAH patients with comorbidities or a more advanced age are less aggressively treated with respect to combination therapy, the outcome of monotherapy in these patients appears to be comparable to that of dual or triple therapy in "typical" PAH patients.

Background:  Implant of indwelling pleural catheters (IPC) represents an established therapy method in addition to pleurodesis for symptomatic recurrent benign and malignant pleural effusions (BPE and MPE).There are only few studies on IPC safety during follow-up, especially with regard to infection and pneumothorax rates.The aim of our investigation was to determine the complication frequency after IPC implant and its predictive factors in patients with BPE vs. MPE., Methods:  Retrospective analysis of all IPC implantations in the pneumology department at the University Hospital Dresden during 2015 - 2018., Results:  An IPC was implanted in 86 patients (43 m/f each; age 66.9 ± 13.3 years) with symptomatic BPE and MPE. BPE and MPE was present in 12.8 % (11/86) and 87.2 % (75/86) of the patients, respectively.A predominantly small and asymptomatic pneumothorax was detectable as an immediate complication in 43/86 (50 %) of patients; 34/43 (79 %) of patients did not require any specific therapy. For 9/43 patients, IPC suction was required for a median period of three days; 8/43 patients had a large pneumothorax with partial or complete regression after a median period of two days.Catheter infection developed in 15.1 % (13/86) of the total group and 36.4 % (4/11) of the BPE vs. 12 % (9/75) of the MPE after a median period of 87 (BPE/MPE 116/87) days. This was more common in BPE (p = 0.035), large pneumothorax (4/8 patients; p = 0.015) and longer catheter dwell times (124 ± 112 vs. 71 ± 112 days; p = 0.07)., Conclusion:  Small pneumothoraxes are frequent after IPC implantation, but usually do not require specific therapy. IPC infection was detected in 15.1 % of all patients after a median period of 87 days. This was more common in patients with BPE, longer catheter dwell times and large pneumothorax., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Chronic granulomatous disease (CGD) should be considered as a differential diagnosis in children and adolescents with frequent infections, especially when caused by certain specific pathogens.This case report describes a 64-year-old female with multiple recurrent and complicated bronchopulmonary infections, caused by common, but also rare pathogens, autoimmune phenomena, malignancies and recurrent organizing pneumonia (OP) with granulomas. Finally, the patient was diagnosed with p47 phox -deficient chronic granulomatous disease (CGD).Individuals with a primary immunodeficiency may survive multiple complications and may be diagnosed at an advanced age especially if the affected structure shows residual activity. When confronted with patients with recurrent bronchopulmonary infections, especially with certain specific rare pathogens, in combination with organizing pulmonary granulomas as well as autoimmune phenomena, CGD should be considered even in elderly patients. Delayed diagnosis significantly increases mortality and morbidity in such cases., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

CPAP is the most common treatment for obstructive sleep apnea.Serious complications from this treatment are very rare. Pneumothorax following lung barotrauma under CPAP therapy has been described in case reports only in patients with pre-existing lung and thoracic diseases.A 68-year-old sleep apnea patient without pre-existing lung or thoracic diseases and with established CPAP therapy since many years was admitted to the hospital after a severe thoracic pain event with persistent shortness of breath. Chest radiograph and computed tomography showed an extensive right-sided pneumothorax with basal bullous emphysema. After surgical treatment of the secondary spontaneous pneumothorax, on the third postoperative day CPAP with reduced pressure was re-introduced with satisfactory sleep apnea findings and without pneumothorax recurrence.As possible cause of pneumothorax in the patient, alveolar inflammatory changes due to over-distention and increased pressure in the alveoli was assumed, which can occur after years of CPAP treatment with gradual pressure increase.In summary, in sleep apnea patients treated with CPAP for years, after sudden onset of thoracic pain and shortness of breath possible spontaneous pneumothorax should be considered., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)