Background Long-term non-invasive ventilation (NIV) has emerged as the standard treatment for patients with chronic hypercapnic COPD. Although regular follow-up visits are recommended to maintain treatment success, the favourable setting for such visits have not yet been investigated. Hypothesis Outpatient follow-up of long-term NIV in stable hypercapnic COPD provides comparable patient benefits. Methods A predefined protocol was used to randomise 113 patients with stable hypercapnic COPD to standard (i) inpatient or (ii) outpatient NIV follow-up (1:1). The primary outcome was the mean difference in health-related quality of life (HRQL) after 12 months, as assessed by the Severe Respiratory Insufficiency Questionnaire (SRI). Patient preference, capillary blood gases, exacerbation rates and mortality, total costs and cost-effectiveness served as secondary outcomes. Results Outpatient NIV follow-up was associated with a non-significant improvement in the SRI Summary Score (SRI-SS) after 12 months (adjusted mean difference 3.7±2.6; p=0.164). PaCO 2 (47.6±10.1 versus 46.5±6.2 mmHg, p=0.906) and NIV adherence (8.3±3.5 versus 8.5±2.3 h; p=0.243) were similar, as were mortality and exacerbations rates. Total annual costs reached € 681 (outpatient) and € 3621 (inpatient). The resulting mean cost difference of –€2940 corresponded to a cost-effectiveness ratio of –€794/SRI point, favouring outpatient care. Outpatient treatment was preferred by most patients (84.3%). Discussion Outpatient NIV follow-up achieved comparable clinical patient outcomes to inpatient care, with a tendency towards better HRQL in the outpatient group. Outpatient follow-up is a safe, more cost-effective approach that is preferred by most patients in a selected population of clinically stable long-term NIV users managed at specialised centres.

Background:Biological sex has a significant impact on the prevalence and course of lung involvement and inflammatory rheumatic diseases (IRD). However, data and analyses addressing this relationship are lacking for Germany. Methods:In a retrospective analysis, data from the German Federal Statistical Office were evaluated using hospital discharge diagnoses coded according to the International Classification of Diseases (ICD-10) from 2005 to 2023. Frequency, temporal trends, and distribution were analysed separately for women and men. Eleven rheumatologic diseases as primary diagnoses were included: rheumatoid arthritis (M05, M06), connective tissue diseases (M32-M35), and ANCA-associated vasculitis (M30.1, M31.3, M31.7). Each was combined with five secondary diagnoses indicating pulmonary involvement (J84.1, J84.8, J84.9, J99.0*, J99.1*). Results:Over the 19-year observation period, the total number of hospitalizations for women with IRD (n = 734,167; 68%) exceeded that of men (n = 349,806; 32%). The absolute number of cases with lung involvement associated with IRD was also higher in women (n = 88,936) than in men (n = 52,523). However, the relative proportion of lung involvement among patients with IRD was higher in men compared to women (15% vs. 12%). In both sexes, case numbers increased steadily over the study period, with a transient decline in 2020. The rise in cases with lung involvement among patients with IRD over time was more pronounced in men. Discussion:The number of hospitalized patients with lung involvement secondary to IRD has increased continuously over the past 19 years. Male patients with IRD appear to have a higher risk of developing lung involvement compared to female patients.

Patient involvement in scientific research is becoming increasingly important to ensure a patient-centered approach to medicine. The objective of this study is twofold: firstly, to ascertain patients’ perspectives on adherence to therapy and secondly, to integrate this information into a systematic review (SR) on interventions to improve adherence in chronic obstructive pulmonary disease (COPD). In parallel with the SR, two focus group interviews with a COPD self-help group were conducted using semi-structured interview guidelines. The interviews were analyzed using computer-assisted qualitative content analysis according to Kuckartz with the aim of complementing the results of the systematic literature review and to develop propositions for further scientific use. The first focus group interview comprising 321 codes included 14 (mean age 67.7 ± 6.8 years; 71.4

Was ist neu? Patient Self-Inflicted Lung Injury (P-SILI) beschreibt ein Konzept, bei welchem sich Patienten in der akuten hypoxämischen respiratorischen Insuffizienz (AHRF) durch einen hohen Atemantrieb und tiefe Atemzüge selbst einen Schaden zuführen und das Lungenversagen perpetuieren können. Die von der Spontanatmung abhängige Lungenschädigung wird wahrscheinlich durch 4 Mechanismen vermittelt: 1. ein erhöhter mechanischer Stress, 2. eine heterogene Ventilation mit Pendelluft, 3. ein gesteigerter pulmonaler Blutfluss mit mikrovaskulären Verletzungen sowie 4. eine Patient-Ventilator-Asynchronität (PVA) im Falle einer nicht-invasive Ventilation (NIV) zur Unterstützung der Spontanatmung. Alle genannten Vorgänge sind eng mit einem gesteigerten Atemantrieb verbunden, welcher sich aus der Pathophysiologie der zugrundeliegenden Lungenschädigung, insbesondere dem Plasmaeintritt in die Alveolen, erklärt. Durch klinische Messverfahren, wie z.B. der Ösophagusdruckbestimmung, ist ein Monitoring der Atemarbeit und des neuronalen respiratorischen Antriebs möglich. Jedoch sind die Messverfahren zum Teil invasiv, in Teilen nicht vollständig validiert, zeit- und materialaufwendig, kostenintensiv und mitunter durch einen mangelnden Patientenkomfort gekennzeichnet. In der Behandlung des akuten Atemversagens (Acute Respiratory Distress Syndrome (ARDS) und AHRF) muss ein P-SILI zwingend vermieden werden. Neuere Daten zeigen, dass ein spätes NIV-Versagen mit nachfolgender Intubation mit den höchsten Mortalitätsraten assoziiert ist. Somit ergibt sich eine patientenindividuelle Einzelfallentscheidung über die zu bevorzugende Beatmungsform, welche regelmäßig auch vor dem Hintergrund eines potenziell möglichen P-SILI sowie eines beatmungsassoziierten Lungenschadens kritisch reevaluiert werden muss. NIV und High-Flow-Sauerstofftherapie (HFNC), Pharmakotherapie sowie die Bauchlage unter Spontanatmung haben Grenzen, die 24/7 neu beurteilt werden müssen. Bislang fehlt die Evidenz großer klinischer Studien bezüglich ihres Einflusses auf die Vermeidung und Behandlung eines P-SILI und des richtigen Zeitpunktes einer Intubation. Als therapeutische Möglichkeiten eines P-SILI kommen nicht-invasive Beatmungsformen wie die Continuous positive airway pressure (CPAP)/NIV-Beatmung oder die HFNC sowie die Pharmakotherapie zur Senkung des Atemantriebs in Betracht.

Abstract:In the treatment of patients with progressive diseases, such as COPD or IPF, there are significant communication gaps across all sectors. Measures to improve communication include advance care planning, determining the patient's wishes, early palliative care, and avoiding unnecessary hospitalization, intensive care, and post-discharge over-treatment, such as long-term invasive ventilation outside of the hospital.

Background Biological sex has a significant impact on the prevalence and course of lung involvement and inflammatory rheumatic diseases (IRD). However, data and analyses addressing this relationship are lacking for Germany. Methods In a retrospective analysis, data from the German Federal Statistical Office were evaluated using hospital discharge diagnoses coded according to the International Classification of Diseases (ICD-10) from 2005 to 2023. Frequency, temporal trends, and distribution were analysed separately for women and men. Eleven rheumatologic diseases as primary diagnoses were included: rheumatoid arthritis (M05, M06), connective tissue diseases (M32-M35), and ANCA-associated vasculitis (M30.1, M31.3, M31.7). Each was combined with five secondary diagnoses indicating pulmonary involvement (J84.1, J84.8, J84.9, J99.0*, J99.1*). Results Over the 19-year observation period, the total number of hospitalizations for women with IRD (n = 734,167; 68%) exceeded that of men (n = 349,806; 32%). The absolute number of cases with lung involvement associated with IRD was also higher in women (n = 88,936) than in men (n = 52,523). However, the relative proportion of lung involvement among patients with IRD was higher in men compared to women (15% vs. 12%). In both sexes, case numbers increased steadily over the study period, with a transient decline in 2020. The rise in cases with lung involvement among patients with IRD over time was more pronounced in men. Discussion The number of hospitalized patients with lung involvement secondary to IRD has increased continuously over the past 19 years. Male patients with IRD appear to have a higher risk of developing lung involvement compared to female patients.

BackgroundAcute respiratory distress syndrome is a heterogeneous syndrome that complicates risk stratification, therapy monitoring and personalised treatment during veno-venous extracorporeal membrane oxygenation. This study aims to identify discrete acute respiratory distress syndrome subphenotypes among veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients using high-resolution electronic health record clustering, and to assess differences in clinical outcomes.Materials and methodsWe conducted a study of 598 adult patients with acute respiratory distress syndrome treated with VV-ECMO. Twenty-six clinically relevant parameters spanning inflammation, coagulation, kidney/liver function, mechanical ventilation, and ECMO parameters were analysed using K-means clustering. Shapley Additive Explanations models were used to identify key differentiating parameters between clusters and independent survival factors. Clinical outcomes were compared between clusters, including treatment duration and survival rates in intensive care.ResultsCluster analysis revealed distinct subphenotypes primarily driven by differences in inflammation (procalcitonin and C-reactive protein), kidney/liver function (creatinine and urea), coagulation (fibrinogen and D-dimer), and mechanical ventilation (positive end-expiratory pressure). Survival rates varied considerably between clusters, most notably within the kidney/liver function (32%) and combined parameter categories (21%). Subphenotypes defined solely by ECMO or ventilator settings showed smaller differences. Intensive care unit length of stay was longer in clusters with multi-organ dysfunction.ConclusionsEarly data-driven clustering of electronic health record parameters identifies clinically meaningful acute respiratory distress syndrome subphenotypes among veno-venous extracorporeal membrane oxygenation patients. Renal, hepatic, and inflammatory dysfunctions are critical determinants of survival. Subphenotype-based stratification may refine risk stratification and management in severe acute respiratory distress syndrome treated with VV-ECMO.

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) requiring invasive mechanical ventilation (IMV) are associated with high mortality and long-term disability. Extracorporeal CO₂ removal (ECCO₂R) using modern high-capacity devices may facilitate early endotracheal extubation and reduce IMV-related complications. To evaluate whether ECCO2R-facilitated early extubation improves clinical outcomes compared with standard IMV in patients with severe AE-COPD requiring IMV. Adults with acute hypercapnic respiratory failure due to AE-COPD requiring IMV who failed or were ineligible for extubation within 24 hours of intubation were randomized to ECCO2R or no ECCO2R. The primary endpoint was a composite of death or severe disability at day 60. 18 patients were randomized before the trial was terminated early by the sponsor for financial reasons (planned enrollment: 192). The primary composite endpoint occurred in 0/8 ECCO2R-treated patients versus 3/9 evaluable IMV-treated patients (33

Abstract:TNF-alpha inhibtors represent an established option for autoimmune disorders such as rheumatoid arthritis, psoriasis and chronic-inflammatory bowel diseases as well as for granulomatous diseases including sarcoidosis. Their primary mode of action is antagonistic, blocking the interaction of TNF-alpha with its receptors TNFR1 and TNFR2. Currently five TNF-alpha inhibitors are clinically used: infliximab, adalimumab, golimumab, certolizumab and etanercept.In rare cases TNF-alpha inhibitors may induce sarcoidosis through a paradoxical reaction. This phenomenon is observed most frequently during treatment with etanercept, although the underlying mechanisms remain unclear. The clinical presentation of TNF-alpha inhibitor-induced sarcoidosis closely resembles that of idiopathic sarcoidosis and is characterized by a heterogeneous, inflammatory and granulomatous disease pattern with affection of multiple organ systems. Depending on the causative active agent, a differing distribution of clinical manifestations may occur.From a diagnostic perspective, laboratory analyses and the histological confirmation of the affected organ demonstrating epithelioid cell granulomas are essential. The cornerstone of therapy is the immediate discontinuation of the triggering TNF-α inhibitor. In selected cases, adjunctive systemic corticosteroid therapy may be considered. With timely recognition and appropriate management, the prognosis is generally favourable.

In the outpatient (i.e., pre- and post-hospital) and inpatient care of patients with chronic progressive diseases, such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), there are serious communication gaps across sectors, particularly regarding advanced care planning and palliative care treatment. Strategies to avoid over-treatment in intensive care are needed.

Abstract:Patient self-inflicted lung injury (P-SILI) describes a pathophysiological concept in which patients with acute hypoxemic respiratory failure (AHRF) may exacerbate lung injury through excessive respiratory drive and vigorous spontaneous breathing efforts, thereby perpetuating respiratory failure. Spontaneous breathing-related lung injury is thought to be mediated by 4 main mechanisms: 1. increased mechanical stress on lung tissue, 2. heterogeneous ventilation with intrapulmonary gas redistribution (pendelluft), 3. augmented pulmonary blood flow leading to microvascular injury, and 4. Patient-ventilator asynchrony (PVA) in the setting of non-invasive ventilation (NIV). All of these mechanisms are closely linked to an elevated respiratory drive, which primarily arises from the underlying lung pathology, particularly alveolar flooding due to plasma leakage. Clinical monitoring of respiratory effort and neural respiratory drive is possible using techniques such as esophageal pressure measurement. However, these methods are often invasive, not fully validated, time- and resource-intensive, costly, and may be associated with reduced patient comfort.In the management of acute respiratory failure, including acute respiratory distress syndrome (ARDS) and AHRF, prevention of P-SILI is essential. Recent evidence suggests that late failure of NIV followed by delayed intubation is associated with the highest mortality rates. Consequently, the choice of ventilatory support must be individualized and continuously reassessed, taking into account the risk of both P-SILI and ventilator-induced lung injury. Non-invasive ventilation, high-flow nasal cannula therapy, pharmacological interventions, and prone positioning during spontaneous breathing all have therapeutic limits that require continuous, round-the-clock evaluation. To date, robust evidence from large clinical trials regarding their impact on the prevention and treatment of P-SILI, as well as the optimal timing of intubation, remains lacking.

Background:Non-invasive ventilation (NIV) is vital for managing chronic hypercapnic respiratory failure in COPD patients, yet the impact of handling issues like mask compliance triggering hospitalisations is often underestimated. Methods:A prospective, monocentric observational study was performed in COPD patients hospitalized for acute exacerbation with established home NIV therapy. Various questionnaires (CAT, SRI, BORG) and blood gas analysis were used to determine the severity and cause of respiratory insufficiency. Results:59 patients (mean age 66.57 years ± 9.42, mean BMI 26.99 ± 8.63) were included. 54.24% were female (n=32). The overall cohort had a mean exacerbation rate of 2.24 ± 1.48 within the last 12 months prior to admission. Patients were divided into 4 sub cohorts based on their exacerbation trigger: infection (n=25), handling problem (n=12), non-infection (n=8), and an overlap cohort with evidence of both handling problem and non-handling problem (n=14). Significant differences exist when comparing exacerbation rate (handling-issue cohort: 2.58 ± 1.68 vs infection cohort: 1.76 ± 1.13, p=0.043), total hospital stay (handling-issue cohort: 9.25 ± 5.94 days vs infection cohort: 12.96 ± 5.76 days, p=0.039). There was no significant difference in health-related quality of life measured by the SRI (Summary Score 40.6±12.3 vs 46.8±14.2; p=0.103). Discussion:In our study, we were able to show that handling problems are associated with frequent exacerbations, cause long hospitalisation periods and are associated with a reduced aspects of quality of life. Patient education and training should therefore play a key role in the treatment of patients.