Severe alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition characterized by low levels of alpha-1 antitrypsin (AAT), leading to progressive lung and/or liver disease. Most severe cases are linked to the Z allele (c.1096G > A (p.Glu366Lys)) of the SERPINA1 gene but characterizing patients with rare mutations remains challenging. This case report discusses the clinical significance of a novel SERPINA1 variant, c.236 T > A (p.Val79Glu; ClinVar accession SCV007334878), and the challenges in profiling such cases. Two male siblings carried both the common Z allele mutation and the novel exon 2 mutation. Despite genetic similarities, their clinical courses diverged. The older brother, a 66-year-old patient, presented with very severe airflow obstruction (GOLD stage IV) and an AAT level of 0.32 g/L. After years of pharmacologic treatment and endoscopic lung volume reduction, his condition worsened, requiring a double lung transplant. In contrast, the younger brother, currently 58 years old, was diagnosed through family screening and had an AAT level of 0.4 g/L. His condition progressed to panlobular basal emphysema accompanied by bronchopathy and mild bronchiectasis, managed with pharmacologic therapy. Both siblings had a history of smoking, potentially influencing their clinical outcomes. This case highlights the complexity of assessing rare SERPINA1 mutations due to underlying biochemical complexities, genetic variability, and diagnostic limitations. It underscores the importance of combining biochemical analysis of variant AAT proteins with clinical evaluation to better understand disease expression, the value of genetic screening in family members, and the need for personalized clinical management to support timely and appropriate therapeutic interventions.

Objective:Description of treatment and prescription patterns among asthma patients in the regions of Magdeburg (MD) and Mannheim (MA) compared nationwide. Methods:We analyzed IQVIATM LRx data 1 from the period of July 2022 to June 2023. The prescription database LRx covers about 80% of prescriptions for patients in the statutory health insurance in Germany. A machine learning model was used to assign the indication of asthma to patients with ≥ 1 redeemed GKV prescription for respiratory diseases. Results:In this analysis, 2992487 patients with asthma were identified in Germany ( MD 20692; MA 55302), of which 30% were assigned to GINA stage 4 (MD 33%; MA 30%) and 4% to GINA stage 5 (MD 5%; MA 5%) (GINA: Global Initiative for Asthma 2). Only 27% of the patients had ≥ 1 prescription from pulmonologists (MD 37%; MA 28%). Among all patients, 13% showed signs of uncontrolled asthma (MD 12%; MA 13%). Of these, 21% were eligible for biologics (Bx) (MD 22%; MA 20%), of which 16% received ≥ 1 Bx prescription (MD 18%; MA 18%). Only 11% of patients with uncontrolled asthma had no acute oral corticosteroid (OCS) prescriptions (MD 10%; MA 9%), whereas among patients continuously treated with biologics, 58% had no OCS prescriptions (MD 68%; MA 75%). Nationwide nearly 24% of continuously with Bx treated patients (MD 24%; MA 31%) redeemed prescription of low to medium dose inhaled corticosteroids (ICS). Conclusion:Patients with severe asthma or signs of uncontrolled asthma require additional care from pulmonologists. Despite all observed regional differences in care, identifying patients with uncontrolled asthma and promptly referring them to pulmonologists is an important approach for improvement. In real-world care, treatment of severe uncontrolled asthma with biologics has the potential to reduce the use of oral and inhaled corticosteroids.

Abstract:PRiVENT (Prevention of Invasive Ventilation through Early Identification and Early Intervention in Patients at Risk) is a cross-sectoral care model developed within the framework of the Innovation Fund of the German Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA). The aim of the project was to identify patients at increased risk of prolonged mechanical ventilation at an early stage and to promote successful weaning from mechanical ventilation through the early involvement of certified weaning centres and structured, interprofessional interventions. By doing so, the project seeks to prevent long-term invasive mechanical ventilation, tracheostomy, and the need for long-term out-of-hospital intensive care.Based on the initial positive results of the Innovation Fund project, a selective integrated care contract pursuant to § 140a of the German Social Code Book V (SGB V) was developed in collaboration with AOK Baden-Württemberg. The objective of this contract was to sustainably transfer the care structures established during the project into routine clinical care and to make them available throughout Baden-Württemberg for insured members of AOK Baden-Württemberg.The core components of the PRiVENT care pathway are the Weaning Board and the Weaning Consultation, both of which are conducted by an interprofessional team consisting of at least a pulmonologist and a respiratory therapist from a certified specialised weaning centre. Consultations may be performed via telemedicine, in a hybrid format, or entirely on site. The following section describes the healthcare services provided within the PRiVENT selective care contract under § 140a SGB V.

Background:The internet is often used as a source of information by patients with sarcoidosis, but its reliability has not yet been comprehensively analysed. The aim of this study was to analyse the content and quality of German-language information on sarcoidosis available on the internet. Methods:All German-language hits from the first 200 search results for "sarcoidosis" on Google, Yahoo, Bing, and YouTube were saved. Two independent investigators evaluated the content (content score with 25 items, 0-25 points) and quality (DISCERN score with 1-5 points, HONCode score with 0-8 points, JAMA score with 0-4 points). Results:128 websites and 12 videos were included. The median time since the last update was 36 and 9 months. The content score was 17 and 13 points, respectively. Quality was rated with a DISCERN score of 2.4 and 2.1 points, the JAMA score of the websites was 2 points, and the HONCode score of the videos was 4.2 points. Blogs achieved poorer results in terms of content (p=0.040) and DISCERN score (p=0.016), while the JAMA score was best for news/media (p=0.002). There were no differences for the videos. Conclusion:Although some German-language information on sarcoidosis found on the internet was adequate in terms of content, its quality was only moderate. It would be desirable to have a reliable and easily recognisable label for adequate information.

BACKGROUND:Transbronchial cryobiopsy has expanded beyond its established role in interstitial lung disease, driven by release of single-use cryoprobes, most notably the 1.1 mm cryoprobe. As use of transbronchial cryobiopsy accelerates across non-interstitial lung disease diagnostic contexts, practice variability has outpaced evidence generation and formal guidance. RESEARCH QUESTION:What are areas of clinical consensus regarding indications, tools, techniques, specimen handling, safety considerations, and requisite procedural expertise for the use of the 1.1 mm cryoprobe in non-interstitial lung disease transbronchial cryobiopsy, including convex-probe endobronchial ultrasound-guided and peripheral pulmonary lesion sampling. STUDY DESIGN AND METHODS:An international panel of bronchoscopy experts was assembled through the Interventional Pulmonology Outcomes Group. Following a structured evidence review, a modified Delphi methodology was conducted, consisting of an initial round of open-ended questions followed by 3 rounds in which panelists rated their agreement with statements on a 5-point Likert scale. Consensus was defined a priori as ≥ 80% agreement. Domains included: (1) peripheral transbronchial cryobiopsy, (2) convex-probe endobronchial ultrasound-guided cryobiopsy, (3) airway, anesthesia, and complication management, and (4) specimen handling and processing. RESULTS:A total of 32 physicians participated in this project. The modified Delphi process consisted of 4 survey rounds conducted between May and November 2025. Consensus was obtained on 31 statements. No consensus was obtained on 17 statements. INTERPRETATION:To our knowledge, this Delphi statement represents the first expert guidance for non-interstitial lung disease applications of both endobronchial ultrasound-guided and peripheral transbronchial cryobiopsy. The consensus statements delineate contemporary best practices, bridge critical gaps in standardization, and outline domains where further research is needed.

Dyspnoea is a highly relevant phenomenon in patients undergoing invasive mechanical ventilation, yet it is often underestimated in clinical practice. Against this background, the European Respiratory Society (ERS) and the European Society of Intensive Care Medicine (ESICM) have published a comprehensive statement on the various aspects of dyspnoea during mechanical ventilation. This article is based on this consensus document and highlights the various dimensions of dyspnoea, from its prevalence and clinical relevance to the individual experiences of patients and its physiological and psychological consequences. It provides a detailed presentation of diagnostic procedures and targeted therapeutic intervention options. Particular emphasis is placed on systematic assessment tools offering valid evaluation approaches for both communicative and non-communicative patients. Additionally, the importance of dyspnoea in relation to lung- and diaphragm-protective ventilation and weaning from mechanical ventilation is discussed.

Introduction Sarcoidosis frequently involves intrathoracic lymph nodes and lung parenchyma and requires histological confirmation for diagnosis. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is recommended for obtaining mediastinal samples, its diagnostic yield frequently necessitates additional transbronchial lung biopsy (TBLB) and/or endobronchial biopsy (EBB). EBUS transbronchial mediastinal cryobiopsy (EBUS-TBMC) can yield larger, well-preserved tissue samples than EBUS-TBNA alone. However, whether EBUS-TBMC alone is equivalent to conventional multimodal sampling (EBUS-TBNA combined with TBLB and/or EBB), and whether TBLB and EBB provide incremental diagnostic value when added to EBUS-TBMC, is still unclear.Methods and analysis In this study, 410 patients with suspected stage I/II sarcoidosis will be randomly assigned in a 1:1 ratio to either the EBUS-TBMC or EBUS-TBNA group. All participants will then undergo TBLB and EBB. The primary outcome will be the granuloma detection rate. The diagnostic sensitivity, negative predictive value and procedure-related complications will be selected for secondary outcomes. Statistical analysis will be performed using SPSS V.24.0, with non-inferior testing for the primary comparison.Ethics and dissemination Approval for this DETECTION-SAR-II trial was obtained by the China-Japan Friendship Hospital Ethics Committee (Ethics number: 2025-KY-075). Participants will be fully informed of objectives, protocol and potential risks of the study before enrolment and will provide written informed consent.Trial registration number NCT07246876.

Zusammenfassung Dyspnoe ist ein hochrelevantes Phänomen bei invasiv beatmeten Patient*innen, das in der klinischen Praxis jedoch häufig unterschätzt wird. Vor diesem Hintergrund haben die European Respiratory Society (ERS) und die European Society of Intensive Care Medicine (ESICM) eine umfassende Stellungnahme zu den unterschiedlichen Aspekten der Dyspnoe unter maschineller Beatmung herausgegeben. Der vorliegende Beitrag beleuchtet auf Basis dieses Konsensdokuments die verschiedenen Dimensionen der Dyspnoe: von der Prävalenz und der klinischen Relevanz bis hin zum individuellen Erleben der Patient*innen sowie den physiologischen und psychischen Konsequenzen. Im Fokus stehen dabei die fundierte Darstellung diagnostischer Verfahren sowie gezielte therapeutische Interventionsmöglichkeiten. Ein besonderer Schwerpunkt liegt auf systematischen Erfassungsinstrumenten, die sowohl für kommunikationsfähige als auch für nicht kommunikationsfähige Patient*innen valide Ansätze zur Einschätzung bieten. Darüber hinaus wird die Relevanz der Dyspnoe im Zusammenhang mit der lungen- und diaphragmaprotektiven Beatmung sowie dem Weaning von der invasiven Beatmung diskutiert.

Pulmonologists have contributed significantly to the detection, diagnosis, and management of lung cancer in the past two decades. Improved understanding of lung cancer epidemiology and risk factors has informed screening programs across the world. Refinements in bronchoscopy have allowed the development of minimally invasive techniques for diagnosis and staging of lung cancer. Technological advances in endoluminal treatments for lung cancer coupled with refinements in navigational bronchoscopy raise the possibility of a one-step diagnosis-staging-treatment for early stage lung cancer. Advances in evaluation and management of malignant pleural effusions have led to better clinical outcomes and quality of life. Better understanding of lung cancer pathogenesis has identified biomarkers that inform cancer risk stratification, application of targeted therapies, treatment-related side effects, and likelihood of recurrence. The growing subspecialization of lung cancer care, coupled with rapid technological and clinical developments, has made essential the multidisciplinary team approach for delivering high-quality, evidence-based care. In this article, an international panel of experts will review the major developments in pulmonary diagnostics in lung cancer in the past two decades. Together, these developments have had a transformative effect on lung cancer care and clinical outcomes. The clinical impact of these developments will be explored, along with future potential for research and innovation, and presented in two parts, first for essential standards and second for emerging innovations.

Zusammenfassung Beschreibung der Behandlungs- und Verordnungsmuster bei Asthma-Patient* innen in den KV-Bezirken Magdeburg (MD) und Mannheim (MA) im bundesweiten Vergleich. Wir analysierten IQVIA LRx-Daten im Zeitraum 7/2022 bis 6/2023. Die Verordnungsdatenbank LRx 1. Zur Zuordnung der Indikation Asthma bei Patient*innen mit ≥ 1 eingelöster GKV-Verordnung für Atemwegserkrankungen wurde ein maschinelles Lernmodell genutzt. Es wurden 2992487 Patient*innen mit Asthma in Deutschland identifiziert (MD 20692; MA 55302), wovon 30 % der GINA-Stufe 4 (MD 33 %; MA 30 %) und 4 % der GINA-Stufe 5 (MD 5 %; MA 5 %) zugeordnet wurden (GINA: Global Initiative for Asthma 2). Nur 27 % wiesen ≥ 1 Verordnung von Pneumolog*innen auf (MD 37 %; MA 28 %). 13 % zeigten Anzeichen von Unkontrolliertheit (MD 12 %; MA 13 %). Von diesen waren 21 % potenziell für Biologika (Bx) geeignet (MD 22 %; MA 20 %), wovon 19 % ≥ 1 Biologika-Verordnung erhielten (MD 21 %; MA 22 %). Nur 11 % der Patient*innen mit unkontrolliertem Asthma hatten keine akuten orale Kortikosteroid (OCS)-Verordnungen (MD 10 %; MA 9 %). Von Patient*innen, die kontinuierlich mit Biologika behandelt wurden, wiesen 58 % (MD 68 %; MA 75 %) keine OCS-Verordnungen auf. Bundesweit wurden etwa 24% (MD 24 %; MA 31 %) dieser Patient*innen mit inhalativen Kortikosteroiden (ICS) in niedriger bis mittlerer Dosierung behandelt. Patient*innen mit schwerem Asthma oder Zeichen von Unkontrolliertheit benötigen eine zusätzliche Versorgung durch Pneumolog*innen. Bei allen beobachteten regionalen Unterschieden in der Versorgung ist die Identifikation von Patient*innen mit unkontrolliertem Asthma und deren rasche Überweisung zu Pneumolog*innen ein wichtiger Ansatzpunkt zur Verbesserung. In der Versorgungsrealität hat eine Behandlung des schweren unkontrollierten Asthmas mit Biologika das Potenzial, den Einsatz oraler und inhalativer Kortikosteroide zu reduzieren.

BACKGROUND:Tobacco use remains a leading cause of preventable morbidity and mortality and is commonly initiated in adolescence. We evaluated whether Smokerface-Poster, a low-intensity, appearance-based school campaign promoting a photoaging app, could attenuate smoking uptake among early adolescents. METHODS:In this two-arm cluster-randomized controlled trial, 126 German secondary schools (9797 grade 6/7 students; 96.0% were 11-13 years old; 51.4% male; 48.6% female) were allocated to intervention or control. Intervention schools displayed two classroom posters for 24 months. Smoking behavior was assessed at baseline and 24 months. As primary outcome, we investigated the between‑group difference in the change in 30-day smoking prevalence, with a number needed to treat (NNT) of < 100 students predefined as clinically relevant per protocol. RESULTS:Baseline smoking prevalence was 7.4% in the control vs. 7.9% in the intervention group. At 24 months post-intervention, smoking prevalence increased by 19.2 %age points in control vs. 18.1 %age points in the intervention group (number needed to treat=93; adjusted ratio of odds ratios 0.87, 95% CI 0.69-1.09; p = 0.228). Favorable, non-significant patterns were also observed for anti-smoking intentions and attitudes. CONCLUSION:Although the between-group difference was not statistically significant, the intervention reached the predefined threshold for clinical relevance, with an NNT of 93. This suggests that, for every 93 students exposed to the Smokerface-Poster campaign, one fewer adolescent would be expected to smoke over the two-year follow-up. Given its low cost of < €50 per 100 students, the intervention appears to be a promising approach to supporting school-based smoking prevention.

Zusammenfassung Das Internet wird häufig als Informationsquelle von Patienten mit Sarkoidose genutzt, die Verlässlichkeit wurde bisher nicht umfassend analysiert. Ziel dieser Studie war es, Inhalt und Qualität von deutschsprachigen Informationen zu Sarkoidose im Internet zu analysieren. Von den jeweils ersten 200 Suchtreffern („Sarkoidose“) bei Google, Yahoo und Bing sowie YouTube wurden alle deutschsprachigen Treffer gespeichert. Zwei unabhängige Untersucher bewerteten Inhalt (Inhaltsscore mit 25 Merkmalen, 0–25 Punkte) und Qualität (DISCERN-Score mit 1–5 Punkten, HONCode-Score mit 0–8 Punkten, JAMA-Score mit 0–4 Punkten). 128 Internetseiten und 12 Videos wurden eingeschlossen. Die mediane Zeit seit dem letzten Update betrug 36 und 9 Monate. Der Inhaltsscore lag bei 17 bzw. 13 Punkten. Die Qualität wurde mit einem DISCERN-Score von 2,4 und 2,1 Punkten bewertet, der JAMA-Score der Internetseiten lag bei 2 Punkten und der HONCode-Score der Videos bei 4,2 Punkten. Blogs erreichten in Bezug auf Inhalt (p=0,040) und DISCERN-Score (p=0,016) schlechtere Ergebnisse, der JAMA-Score war bei Nachrichten/Medien am besten (p=0,002). Für die Videos ergaben sich keine Unterschiede. Deutschsprachige Informationen zur Sarkoidose im Internet zeigten zwar einen teilweise ausreichenden Inhalt, schnitten qualitativ aber nur mäßig ab. Eine verlässliche und schnell zu erkennende Kennzeichnung adäquater Informationen ist wünschenswert.

INTRODUCTION:Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated. METHODS:We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31-54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method. RESULTS:In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs. CONCLUSIONS:Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.

Chest quantitative computed tomography (QCT) has been used in clinical trials to monitor patients with alpha-1 antitrypsin deficiency (AATD). There is limited data on the use of quantitative computed tomography (QCT) to phenotype emphysema in AATD. Data from patients with a reduced AATD serum level and/or at least one deficiency mutation, who underwent a chest CT scan at the Thoraxklinik, University of Heidelberg, between 03/2012 and 02/2024, were retrospectively analyzed. The patients were categorized into three groups based on their AAT serum levels: reduced to normal (> 70 mg/dl), moderate (41–70 mg/dl), and severe (≤ 40 mg/dl). The QCT analyses were performed using a fully automated quantitative CT software package (YACTA v2.9.4.98). In this retrospective cohort study, 75 AATD patients were analysed, including 13 with reduced-to-normal AATD, 16 with moderate AATD and 46 with severe AATD. The mean age was 54.3 ± 14.7 years with no differences between groups. Significant differences in pack-years (PY) were found: reduced to normal 14.9 ± 17.2, moderate 39.4 ± 31.9 and severe 15.1 ± 14.6 (p < 0.001). There were no differences in predicted FEV1