Post-COVID syndrome (PCS) refers to persistent or new-onset symptoms 3 months after SARS-CoV-2 infection lasting for at least 2 months. The characterization of PCS varies across studies, with a substantial heterogeneity regarding different study samples, survey instruments, and follow-up periods. This is particularly the case in hospitalized patients vs. outpatients, as well as regarding different variants of concern (VOCs) and their impact on the frequency and severity of specific symptoms. The study population of Beyond COVID was recruited in six German cities by inviting (1) individuals registered as SARS-CoV-2 PCR positive at the local Public Health Authorities and (2) previously hospitalized patients with infection date after 1st March 2021. Participants were allocated to the predominant VOC of their first infection. Questionnaires to assess pre-existing conditions, symptoms during infection, and persisting symptomswere performed. Follow-up at sixth-month intervals is planned for 3 years. The study is ongoing. This publication describes the parameters at the baseline visit (BV). We included 1257 participants (13

INTRODUCTION:Sex-related differences in interstitial lung disease (ILD) phenotypes are well recognized, but it remains unclear whether sex itself independently influences outcomes in non-idiopathic pulmonary fibrosis (non-IPF) ILD once comorbidities, lung function, and treatment are considered. METHODS:In the prospective INSIGHTS-ILD registry (data cut 17 September 2025), we compared men and women with non-IPF ILD using descriptive analyses and Cox models with prespecified adjustment steps: model A (age, comorbidity count, and smoking), model B (A + forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]), and model C (B + antifibrotic therapy). Prespecified subgroup analyses included age strata (≤55 and >55 years) and ILD entities. Longitudinal FVC and DLCO trajectories were assessed over 24 months. RESULTS:Among 883 patients (483 men and 400 women), exposures and disease entities differed significantly by sex: men reported more occupational/environmental exposures and had higher rates of fibrotic idiopathic interstitial pneumonia, whereas women more frequently had autoimmune-related ILD and a family history of ILD. Men had a higher comorbidity burden and more often received antifibrotic therapy at baseline. Survival was shorter in men (HR: 1.51; 95% CI: 1.03-2.21), but this association disappeared after adjustment in model A (HR: 1.04; 95% CI: 0.65-1.68), model B (HR: 1.03; 95% CI: 0.61-1.74), and model C (HR: 1.04; 95% CI: 0.62-1.77). Progression-free survival and transplant-free survival showed no consistent sex-related differences. Longitudinal FVC and DLCO declines were modest and largely parallel in both sexes, with no significant between-group differences. Findings were similar across age groups and ILD entities. CONCLUSION:Men and women with non-IPF ILD differ in exposures, phenotypes, and comorbidities, but after accounting for these factors, sex is not an independent predictor of survival or functional progression. Risk assessment should therefore primarily be based on objective disease characteristics rather than sex alone.

Background: Systemic thrombolysis for intermediate-high and high-risk pulmonary embolism (PE) is limited by major bleeding risk. Ultrasound-facilitated catheter-directed thrombolysis (USAT) enables targeted fibrinolysis with lower thrombolytic doses, but comparative effectiveness data are often confounded by selection bias. We aimed to evaluate the safety and efficacy of USAT versus conventional therapy (anticoagulation or systemic thrombolysis) in a propensity score-matched cohort of patients managed within a multidisciplinary Pulmonary Embolism Response Team (PERT) pathway. Methods: We performed a retrospective study of 230 consecutive patients within a multidisciplinary PERT pathway. Patients received USAT using the EkoSonic Endovascular System or conventional therapy consisting of anticoagulation or systemic lysis. One-to-one propensity score matching (PSM) was performed, adjusting for age, sex, Pulmonary Embolism Severity Index (PESI), chronic kidney disease, history of deep vein thrombosis, obesity, and baseline troponin. A doubly robust logistic regression (PSM plus regression adjustment) was used to account for residual imbalance in left heart failure. Results: PSM yielded 81 matched pairs. USAT was associated with significantly lower in-hospital mortality (2.5% vs. 17.3%, P=0.003) and shorter hospital stay (13.0 vs. 17.5 days, P=0.008). Doubly robust post-match logistic regression confirmed USAT as an independent predictor of survival (adjusted odds ratio 0.17, P=0.007). Regarding safety, USAT had significantly fewer International Society on Thrombosis and Hemostasis (ISTH) major bleeding events (1.2% vs. 11.1%, P=0.02), whereas clinically relevant non-major bleeding was more common (17.3% vs. 1.2%, P<0.001). In exploratory subgroup analysis of obese patients (body mass index >30 kg/m(2)), USAT showed a similar mortality signal (3.1% vs. 33.3%, P=0.02). Conclusions: USAT was associated with lower in-hospital mortality and shorter hospital stay compared with conventional therapy. USAT was also associated with fewer major bleeding events, whereas clinically relevant non-major bleeding was more frequent. Exploratory subgroup analysis in obese patients suggested a similar mortality signal.

Background:Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority. Objectives:To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs. Design:Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19. Setting:Contributed data were collected in clinical, community and research settings. Interventions:Interventions from original studies were included as covariates in models. Data sources:MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019-November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers. Methods:Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3-6 months, 9-12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I2. Outcome measures:Included overall perception of health, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder, fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life. Results:PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants' median age was 58 years interquartile range (45-68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality. Limitations:Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system. Conclusions:PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities. Future work:Evidence gaps included healthcare resource use, isolation, loneliness, societal participation and return to work outcomes. Data are needed on the role of health inequity on long-term outcomes. Study registration:This study is registered as PROSPERO (CRD42020224323, IRAS ID: 293578). Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132895) and is published in full in Health and Social Care Delivery Research; Vol. 14, No. 29. See the NIHR Funding and Awards website for further award information.

Background Despite the established use of long-term oxygen therapy (LTOT) for chronic respiratory diseases, a simple tool to assess LTOT use, clinical effectiveness and side effects is not currently available. We therefore designed and developed the Questionnaire for Oxygen Therapy Evaluation (QuOTE). Methods Delphi methodology was used by a group of international respiratory specialists to identify the domains and questions to include in the questionnaire. The questionnaire was beta-tested by a group of patients using LTOT. Results In the first round, 13 clinical and academic respiratory clinicians agreed the domains to be included. Questions covered physical activity, dyspnoea, sleep quality, mental clarity, LTOT side effects, use patterns and equipment. Advantages and disadvantages of current tools, clinical assessment priorities for patients and clinicians and the caveats and advantages around length were discussed, further supported by the results of a confirmatory systematic literature review. 3 rounds of Delphi consensus method focused 18 questions to 9 questions. Usability tests for all but 3 patients reported the questionnaire was easy to understand, only 2 felt it was not quick and easy to complete and only 1 patient needed assistance to complete the 9 question QuOTE.

Purpose:Fractional exhaled nitric oxide (FeNO) is an important biomarker that is used to phenotype patients with (severe) asthma. This study evaluated the effect of chewing gum on FeNO values. Patients and Methods:Patients with stable asthma and elevated FeNO (≥25 ppb) were randomised to the control group (no chewing gum) or to chew gum for 15 minutes after a baseline FeNO measurement. A second FeNO measurement was performed 15 minutes after the first. The primary endpoint was the change in FeNO from baseline to 15 minutes. Results:Thirty patients with asthma (15 male, age 52±15 years) were randomised to the control or chewing gum group. Clinical characteristics, medications, laboratory testing and pulmonary function did not differ significantly between the two groups. The change in FeNO from baseline to 15 minutes was -3.3 ppb in the chewing gum group (p=0.02 vs. baseline) and +3.2 ppb in the control group (p=0.003 vs. baseline); the between-group difference for this change (median -13% in the chewing gum group vs. median +7% in the control group) was statistically significant (p=0.001). Conclusion:The present study showed for the first time that chewing gum influences FeNO measurement in patients with asthma. This is clinically relevant because FeNO is an important biomarker for the diagnosis, phenotyping and antibody-based treatment of asthma. Based on our findings, patients should be advised not to chew gum before the measurement of FeNO.

Zusammenfassung Die Aerosoltherapie ist ein essenzielles Verfahren in der Behandlung akuter und chronischer Atemwegserkrankungen. Derzeit existiert keine aktuelle Leitlinie aus den deutschsprachigen Ländern zur Auswahl und Anwendung von Verneblersystemen bei Patienten unter High-Flow-Therapie via Nasenkanüle (HFT) und nichtinvasiver Beatmung (NIV). Ein interdisziplinäres Expertengremium aus Pneumologen und Intensivmedizinern entwickelte praxisorientierte Empfehlungen zur Aerosoltherapie unter HFT und NIV. Die Evidenzgrundlage bildete eine systematische Recherche in der Datenbank PubMed der US National Library of Medicine bis einschließlich November 2025.Einbezogen wurden Publikationen zu klinischen Studien, Übersichtsarbeiten, Leitliniendokumente und technische Berichte. Der jeweilige Evidenzgrad der Informationen wurde bewertet. Die Empfehlungen wurden in einem Mehrstufenverfahren konsentiert. Die Aerosolapplikation unter HFT und NIV mit einem Vibrating-Mesh-Vernebler (VMN) führt zu einer besseren Lungendeposition im Vergleich zur Verwendung eines Jet Nebulizers (JN). Ein JN ist geeignet, wenn VMN nicht verfügbar sind, hochvisköse Medikamentenlösungen vernebelt werden sollen oder wenn budgetäre Limitationen bestehen. Die Wahl und Anwendung des Verneblersystems sollte patientenindividuell, indikationsbezogen und unter Berücksichtigung technischer, klinischer und ökonomischer Rahmenbedingungen erfolgen.

OBJECTIVES:Acute intermediate-high-risk pulmonary embolism (PE) is associated with right-ventricular (RV) dysfunction, biomarker elevation, and risk of early clinical deterioration. Ultrasound-assisted catheter-directed thrombolysis (USAT) using the Eko Sonic Endovascular System (EKOS) system is increasingly used in selected patients; however, real-world data on physiological response and clinically relevant in-hospital outcomes remain limited. METHODS:We conducted a retrospective single-centre analysis of 128 consecutive patients with acute intermediate-high-risk PE treated with EKOS-guided USAT within a structured Pulmonary Embolism Response Team (PERT) pathway between August 2017 and December 2023. Changes in RV/LV ratio, B-type natriuretic peptide (BNP), and cardiac troponin before and after intervention were assessed. A composite end-point of death, extracorporeal membrane oxygenation (ECMO), renal replacement therapy, or invasive mechanical ventilation captured clinically meaningful deterioration. Multivariable logistic regression identified determinants of the composite end-point. RESULTS:RV/LV ratio and biomarkers improved significantly after intervention. Median RV/LV ratio decreased from 1.6 to 1.0, and BNP declined from 2365 to 877 pg/mL (both P < .001). Clinically meaningful in-hospital deterioration requiring escalation of organ support occurred in a subset of patients and was predominantly associated with baseline disease severity. Short-term survival remained favourable (60-day probability 96.9%). CONCLUSIONS:In this real-world, PERT-guided cohort, EKOS was associated with rapid physiological improvement and favourable short-term survival in patients with intermediate-high-risk PE. These findings should be interpreted as descriptive single-centre experience.

Background Long COVID refers to persistent or new-onset symptoms three months after SARS-CoV-2 infection lasting for at least two months. The prevalence of Long COVID ranges across studies, while the associated risk factors are not well understood. Methods The study population of Beyond COVID was recruited in six German cities by inviting (1) individuals registered as SARS-CoV-2 PCR positive at the local Public Health Authorities and (2) previously hospitalized patients with infection date between 1st March 2021 and 31st May 2022. Participants were allocated to the predominant variant of concern (VOC) of their first infection. Blood exams and questionnaires to assess persisting symptoms, quality of life (QOL), and psychosocial factors were performed. This publication describes the parameters at baseline visit (BV). Results We included 1258 participants (13.4% hospitalized-based; 86.6% population-based). Most participants had BA.2 (34.6%), followed by Delta (26.8%), BA.1 (18.9%), and Alpha (17.3%). The mean age was 47.1, and 59% were female. 68.8% reported at least one persisting symptom. Fatigue was the most frequent ongoing symptom (32.8%), followed by concentration disorders (25.4%) and dyspnoea (22%). Female sex, lower education, and a shorter period between infection and BV were associated with higher rates of persisting symptoms and symptom-severity. BA.1 and BA.2 had lower rates of persisting symptoms and symptom severity. Conclusion Analysis of baseline data from the Beyond-COVID cohort confirms a high percentage of persistent symptoms. Omicron variants had lower rates of persistent symptoms and symptom severity. Long-term follow-up of study participants will contribute to the characterization of Long COVID.

Background:Aerosol therapy is an essential procedure in the treatment of acute and chronic respiratory diseases. Currently, there are no up-to-date guidelines from German-speaking countries on the selection and use of nebulizer systems in patients undergoing high-flow therapy via nasal cannula (HFT) and non-invasive ventilation (NIV). Methods:An interdisciplinary panel of experts consisting of pulmonologists and intensive care physicians developed practice-oriented recommendations for aerosol therapy under HFT and NIV. The evidence base was derived from a systematic search of the PubMed database of the US National Library of Medicine up to and including November 2025.Publications on clinical studies, reviews, guideline documents, and technical reports were included. The respective level of evidence of the information was evaluated. The recommendations were agreed upon in a multi-stage process. Results:Aerosol administration under HFT and NIV with a vibrating mesh nebulizer (VMN) achieved better lung deposition compared to the use of a jet nebulizer (JN). A JN is suitable if VMNs are not available, if highly viscous drug solutions are to be nebulized, or if there are budgetary limitations. Conclusion:The choice and application of the nebulizer system should be patient-specific, consistent with the indication, taking into account technical, clinical, and economic requirements.

Die Entwöhnung von der Beatmung kann im Rahmen der intensivmedizinischen Therapie einen erheblichen Zeitraum in Anspruch nehmen und die Verlegung auf eine spezialisierte Weaning-Station erforderlich machen. Bislang liegen nur wenige Daten in Bezug auf Parameter vor, die bei Patienten im prolongierten Weaning mit dem Überleben bzw. mit Entwöhnbarkeit von der invasiven Beatmung assoziiert sind. Es wurden die Therapieverläufe von n=659 Patienten, die auf der Weaning-Station der Uniklinik RWTH Aachen in einem Zeitraum von 8 Jahren behandelt worden waren, retrospektiv ausgewertet. In der multivariaten Analyse bezüglich des Überlebens der Patienten zeigte sich eine inverse Assoziation mit dem Lebensalter (OR 0,958; p<0,001), vorbestehender onkologischer Erkrankung (OR 0,422; p=0,008) oder chronischer Niereninsuffizienz (OR 0,509; p=0,035), kumulativer Flüssigkeitsbilanz (OR 0,948; p<0,001) und Laktatspiegel (OR 0,528; p=0,032). In Bezug auf die erfolgreiche Entwöhnung von der invasiven Beatmung fanden sich entsprechende inverse Assoziationen für Lebensalter (OR 0,975; p=0,021), chronische Niereninsuffizienz (OR 0,382; p=0,001), kumulative Flüssigkeitsbilanz (OR 0,953; p<0,001) und Laktat (OR 0,349; p<0,001). Zusätzlich waren eine bestehende neuromuskuläre Erkrankung (OR 0,212; p=0,01), die Beatmungsdauer auf der Intensivstation (OR 0,98; p=0,015) und die Bikarbonatkonzentration (OR 0,947; p=0,049) mit erfolglosem Weaning assoziiert. Zusammengefasst konnten an einem großen Kollektiv verschiedene Parameter identifziert werden, die mit dem Überleben bzw. erfolgreicher Beatmungsentwöhnung von Patienten im prolongierten Weaning assoziiert sind.

Proenkephalin A 119–159 (PENK) is a promising functional kidney biomarker, evaluated in various clinical settings. In critical care medicine, early diagnosis of acute kidney injury (AKI) is crucial; however, to date, the diagnosis and the assessment of kidney function is still based on serum creatinine (sCr) and urine output, both associated with several limitations. Between November 2020 and March 2022, we implemented PENK in our daily practice on our intensive care units (ICU). PENK, sCr, AKI stage, and the start and duration of renal replacement therapy (RRT) were documented. Almost 18,000 PENK measurements from 4169 patients were analyzed, and the glomerular filtration rate (GFR) was estimated with the new PENK-GFR formula. PENK outperformed sCR in the kidney function assessment and sCR trajectory over time. Moreover, PENK predicted the use of RRT and thus showed its usefulness in critical care daily practice.

The german guideline on non-invasive ventilation offers comprehensive recommendations for the treatment of chronic respiratory failure in various underlying conditions, such as COPD, thoraco-restrictive diseases, obesity-hypoventilation syndrome, and neuromuscular diseases. The aim of the guideline is to improve the treatment of patients with chronic respiratory insufficiency using non-invasive ventilation and to make the indications and therapy recommendations accessible to all involved in the treatment process. It is based on the latest scientific evidence and replaces the previous guideline from 2017. This revised guideline provides detailed recommendations on the application of non-invasive ventilation, ventilation settings, and the subsequent follow-up of treatment. In addition to the updated evidence, important new features of this guideline include new recommendations on patient care and numerous detailed treatment pathways that make the guideline more user-friendly. Furthermore, a completely revised section is dedicated to ethical issues and offers recommendations for end-of-life care. This guideline is an important tool for physicians and other healthcare professionals to optimize the care of patients with chronic respiratory failure.

Introduction In 2021, the Global Lung Initiative (GLI 2021) network recommended new static volume lung function reference equations, setting new normal ranges for lung hyperinflation indices and, as as result, for the classification of lung hyperinflation severity. This study examined how use of the GLI 2021 reference equations affected the detection of lung hyperinflation and the distribution of lung hyperinflation severity based on the lung hyperinflation severity grading scale, which relies on fixed % predicted cut-offs and z-scores. Methods An analysis was performed on data from 12 535 body plethysmography recordings performed from January 2013–June 2023. The GLI 2021 and the European Community for Steel and Coal working party (ECSC) reference equations were used to calculate the z-scores for residual volume (RV), total lung capacity (TLC), and RV/TLC. The % predicted RV/TLC ratios were calculated and the distribution of lung hyperinflation severity grading was assessed. Results Using % predicted cut-offs, severe lung hyperinflation was observed more frequently using GLI 2021 compared with the ECSC reference equation (27% versus 8.8%, p<0.001), while mild lung hyperinflation was identified in 7% of the recordings using GLI 2021 ( versus 21% using ECSC; p<0.001). Grading using the GLI 2021 reference equation and z-scores produced a similar distribution of lung hyperinflation severity to the use of % predicted cut-offs and ECSC reference equations. Discussion The study highlights a significant difference in lung hyperinflation grading using GLI 2021 reference equations, necessitating review of the severity scale when using %predicted cut-offs and z-scores with GLI 2021 reference equations.