Journal of Radioanalytical and Nuclear Chemistry

Gülsen A.

Background: Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up. Objective: This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD. Methods: The study included US patients with COPD who were seen between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β2-agonist (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes occurring after initiation of dupilumab versus LABA-containing therapies was measured. For detailed methods, please see the Methods section in this article’s Online Repository at www.jacionline.org. Results: A total of 1521 dupilumab initiators and 1521 propensity score-matched patients who were receiving LABA-based therapies were included. Receiving dupilumab was associated with lower all-cause mortality (hazard ratio [HR] = 0.53, 95% CI = 0.43-0.65), fewer emergency department visits (HR = 0.78, 95% CI = 0.69-0.89), and lower acute exacerbation rates (HR = 0.59, 95% CI = 0.53-0.65). Dupilumab was also associated with reductions in the requirement for short-acting β2-agonists (HR = 0.48, 95% CI = 0.43-0.52) and short-acting muscarinic antagonists (HR = 0.43, 95% CI = 0.37-0.49) for symptom control. Additionally, dupilumab decreased rates of subsequent pneumonia (HR = 0.65, 95% CI = 0.50-0.86), and COPD-relevant comorbidities, including new-onset heart failure (HR = 0.69, 95% CI = 0.53-0.90) and new-onset anxiety (HR = 0.70, 95% CI =0.53-0.93). Conclusions: In patients with COPD, dupilumab was associated with a lower mortality rate, fewer emergency department visits, and a reduced risk of acute exacerbations, respiratory symptoms, and respiratory infections. More studies are needed to validate the efficacy of dupilumab among patients with COPD of various severities.

Stanzel F.

Die Studie untersuchte die diagnostische Ausbeute verschiedener Methoden zur Abklärung eines exsudativen Pleuraergusses. Analysiert wurden die Zytologie, der Zellblock und die geschlossene Pleurabiopsie, sowohl einzeln als auch in Kombination. In einer retrospektiven Untersuchung an 175 Patienten in Thailand (2014–2020) wurden 138 maligne (78,9%) und 34 tuberkulöse (19,4%) Pleuraergüsse diagnostiziert. Die diagnostische Ausbeute betrug für die Zytologie 40,6%, für den Zellblock 36,0% und für die geschlossene Pleurabiopsie 58,3%. Die Kombination der Zytologie mit dem Zellblock verbesserte die Trefferquote um 49,1%, während die Kombination aller drei Methoden die diagnostische Ausbeute um 81,1% erhöhte. Besonders bei malignen Pleuraergüssen stieg die Detektionsrate durch die Kombination auf 85,5%. Komplikationen traten bei 10% der Patienten auf, darunter ein Pneumothorax in 6,9% der Fälle. Die Ergebnisse zeigen, dass die Kombination aus geschlossener Pleurabiopsie, Zellblock und Zytologie eine hohe diagnostische Effizienz bietet.

Watz H.

Frohnhofen H.

Background/Objectives: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality in the United States (U.S.), with rates varying by disease severity, comorbidities, and sociodemographic factors. Cognitive impairment has been independently associated with increased mortality, but has not been well studied in relation to COPD despite being a frequently overlooked comorbidity in COPD patients. The purpose of this nationwide study was to assess the relationship between low cognitive performance and the risk of mortality among older adults with COPD while adjusting for major sociodemographic and health-related characteristics. Methods: This study utilized the 1999-2002 National Health and Nutrition Examination Survey (NHANES) and the respiratory mortality data of noninstitutionalized US adults aged over 65 years. Survival curves showing the combined effect of cognitive decline and COPD using the Kaplan-Meier product-limit method to estimate the percent survival of the subject at each point in time were used. Results: The final sample included 2013 older adults, with 39.1% showing low cognitive performance and 12.7% having COPD. Those with low cognitive performance were older, less educated, had lower income, were more likely to be racial/ethnic minorities, and had a history of cardiovascular diseases (CVD); they were also more likely to have COPD or chronic kidney disease (CKD). The adjusted hazard ratio for respiratory-related mortality risk was highest for individuals with both COPD and low cognitive performance (hazards ratio = 8.53), people with COPD alone also had a higher respiratory-related mortality risk (hazards ratio = 4.92), but low cognitive performance alone did not significantly increase respiratory-related mortality risk.

Knoch J.

Background: This study was to examine the association between treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the risk of developing ventilator-associated pneumonia (VAP) among patients receiving mechanical ventilation (MV) in the intensive care unit (ICU). Methods: Utilizing a retrospective cohort approach, the data were extracted from the Medical Information Mart for Intensive Care IV database. VAP diagnoses were ascertained through the international classification of disease codes recorded in the database. Both univariate and multivariable logistic regression analyses were conducted to assess the association between ACEI or ARB use and VAP. Subgroup analyses were performed to evaluate the impact of comorbidities (AKI, renal failure, diabetes, hypertension, and sepsis), simplified acute physiology score II (SAPS II), as well as the use of vasopressors and antibiotics on this association. Odds ratios (ORs) with 95% confidence intervals (CIs) were used as the evaluation metrics. Results: The study comprised 8,888 patients, with 897 (10.09%) experiencing VAP. The analysis revealed that patients on ACEI or ARB therapy had a lower risk of developing VAP (OR: 0.79, 95% CI: 0.62–0.99, P = 0.047). Subgroup analyses revealed that the protective effect was observed in patients with AKI (OR: 0.70, 95% CI: 0.52–0.94, P = 0.020), renal failure (OR: 0.14, 95% CI: 0.02–0.84, P = 0.032), and diabetes (OR: 0.64, 95% CI: 0.43–0.94, P = 0.024), as well as in those receiving vasopressors (OR: 0.67, 95% CI: 0.49–0.92, P = 0.012), and antibiotics (OR: 0.74, 95% CI: 0.57–0.96, P = 0.021). No significant difference in VAP development was observed between patients treated with ACEI versus ARB (OR: 0.84, 95% CI: 0.49–1.47, P = 0.547).

Schnoy E.

Introduction: We aim to investigate the contribution of interstitial lung disease (ILD) to mortality in patients with inflammatory bowel disease (IBD). Methods: We performed a comprehensive retrospective, population-based epidemiological study across the United States from 2001 to 2020, using the Wide-ranging Online Data for Epidemiologic Research database. Mortality data were classified according to the International Classification of Diseases, Tenth Revision, with the codes J84 for ILD, K50 for Crohn’s disease, and K51 for ulcerative colitis. To discern patterns, age-adjusted mortality rates (AMR) were computed, stratified by sex, geographic census region, and racial/ethnic demographics. Results: From 2001 to 2020, there were 57,967 reported deaths among patients with IBD with an AMR per million significantly rising from 10.989 in 2001–2005 to 11.443 in 2016–2020 (P < 0.0001). ILD was a contributor to death in 1.19% (692/57,967) of these cases, with AMR rising from 0.092 to 0.143 per million (P = 0.010). The percentage of ILD-related deaths in the IBD population increased from 1.02% to 1.30% over 2 decades. ILD was a more common cause of death in patients with Crohn’s disease than with ulcerative colitis (54.6% vs 45.4%), with a significant increase for both conditions from 2001 to 2020 (P < 0.05). An upward trend in ILD-related mortality was observed in both sexes (P < 0.05) and within the White population (P = 0.010).

Aringer M.

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies. Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review. The evidence derived was discussed and overarching principles, recommendations and future research agenda were iteratively developed with voting rounds. Results: The task force agreed on 22 recommendations covering 8 clinical/organ domains including Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis, skin fibrosis, interstitial lung disease (ILD), gastrointestinal manifestations and arthritis. Most new recommendations are related to skin fibrosis and ILD. These included novel recommendations for the use of mycophenolate mofetil, nintedanib, rituximab and tocilizumab for the treatment of these crucial disease manifestations. The recommendations also included first-line and second-line interventions, providing increased utility for rheumatology practitioners. Important additions to the future research agenda included consideration of novel interventions for the management of vascular, musculoskeletal and gastrointestinal manifestations and calcinosis, as well as for the local management of digital ulcers. Conclusion: These updated recommendations include the first set of synthetic and biological targeted therapies recommended for key fibrotic manifestations of SSc as well as first-line combination treatment for newly diagnosed pulmonary artery hypertension and prioritise a new research agenda for the coming years.

Sticherling M.

Objective: Identify the clinical characteristics and prognostic factors in patients with idiopathic inflammatory myopathy (IIM) combined with interstitial lung disease (ILD). Methods: IIM-ILD patients who were hospitalized at Guangxi Medical University from January 2017 to December 2022 were retrospectively analyzed and classified as having dermatomyositis (DM)-ILD or -ILD. Clinical and laboratory results were analyzed. Results: There were 39 males and 111 females, the mean age of disease onset was 50.4 ± 12.3 years, and the median disease duration was 3 months (range: 1–6). Ninety-seven patients had DM-ILD, and 53 had ASS-ILD. The DM-ILD group had 72% positivity for the anti-MDA5 antibody and 5.2% positivity for the anti-Mi-2 antibody; the ASS-ILD group had 67.9% positivity for the anti-Jo-1 antibody and 17% positivity for the anti-EJ antibody. Muscle symptoms, skin ulcers, rash, rapidly progressing interstitial lung disease (RP-ILD), and elevated levels of serum carcinoembryonic antigen were more common in DM-ILD patients (all p < 0.05). However, pericardial effusion and pleural effusion, elevated creatinine kinase, and elevated C-reactive protein were more common in ASS-ILD patients. After a median follow-up of 15.5 months, there were more deaths in the DM-ILD group (42.3% vs. 13.2%, p < 0.001). Multivariate Cox regression analysis showed that RP-ILD, dyspnea, and the usual interstitial pneumonia type of ILD had negative associations with overall survival (OS), and arthralgia had a positive association with OS (all p < 0.05).

Freund O., Wand O., Kutzkel S., Tiran B., Pumin I., Regev I.F., Levy L., Bar-Shai A.

Hintergrund: In den letzten Jahrzehnten wurde in verschiedenen randomisierten kontrollierten Studien (RCT) die Wirksamkeit biologischer Therapien für COPD untersucht. Dennoch wurde in diesem Bereich noch keine Auswertung von Real-World-Daten und Kennzahlen bezüglich Patienten-berichteter Outcomes (PROM) durchgeführt. In der vorliegenden Arbeit stellen wir eine systematische Literaturübersicht der Real-World-Daten und PROM von biologischen Behandlungen für COPD vor. Methoden: Für die systematische Literaturübersicht wurden 3 große Datenbanken (MEDLINE/PubMed, Scopus und ScienceDirect) herangezogen. Eingeschlossen wurden klinische Studien (RCT, Kohortenstudien, Fallserien/-berichte), in denen COPD-Patienten, die mit einer biologischen Therapie behandelt wurden, evaluiert wurden. Ergebnisse: Die Übersicht ergab 12 geeignete Studien (9 RCT und 3 «Real-World»-Fallserien/-berichte). Die Bewertung der PROM in den eingeschlossenen Studien beschränkte sich hauptsächlich auf die Schwere der Atemwegssymptome und die damit einhergehende Belastung. Die meisten biologischen Therapien gingen mit verbesserten PROM im Vergleich zur Baseline einher, allerdings nicht bei Placebo. Dupilumab war sowohl bei objektiven als auch bei subjektiven Messungen die einzige biologische Therapie mit in RCT nachgewiesener Wirksamkeit. Eine frühere Studie berichtete über die von den Patienten selbst wahrgenommenen Arzneimittelwirkungen, während keine Studie den wahrgenommenen Krankheitszustand der Patienten evaluierte. Nur 25 Patienten wurden in einem Real-World-Setting auf alle biologischen Therapien zusammen beurteilt. Die Real-World-Daten waren retrospektiv in Form von Fallberichten oder -serien.

Ramakrishnan S., Russell R.E., Mahmood H.R., Krassowska K., Melhorn J., Mwasuku C., Pavord I.D., Bermejo-Sanchez L., Howell I., Mahdi M., Peterson S., Bengtsson T., Bafadhel M.

Hintergrund: Exazerbationen von Asthma und chronisch-obstruktiver Lungenerkrankung (COPD) sind wichtige Ereignisse, die mit kritischen Erkrankungen einhergehen. Die eosinophile Entzündung ist ein behandelbares Symptom, das häufig bei akuten Exazerbationen von Asthma und COPD auftritt. Wir stellten die Hypothese auf, dass bei Patienten mit eosinophilen Exazerbationen eine einmalige Injektion von Benralizumab, einem humanisierten monoklonalen Antikörper, der gegen den Interleukin-5-Rezeptor alpha gerichtet ist, allein oder in Kombination mit Prednisolon die klinischen Ergebnisse im Vergleich zur Standardbehandlung mit Prednisolon verbessert. Methoden: Bei der Studie «Acute exacerbations treated with BenRAlizumab» (ABRA) handelte es sich um eine multizentrische, doppelblinde, placebokontrollierte, randomisierte Phase-2-Studie, die in Großbritannien am Oxford University Hospitals NHS Foundation Trust und am Guy’s and St Thomas’ NHS Foundation Trust durchgeführt wurde. Die Patienten wurden in den Notfallambulanzen und Notaufnahmen dieser beiden Krankenhäuser rekrutiert. Zum Zeitpunkt einer akuten Exazerbation von Asthma oder COPD wurden Erwachsene mit einer Eosinophilenzahl im Blut von 300 Zellen/μl oder mehr im Verhältnis 1:1:1 randomisiert: für eine Akutbehandlung mit Prednisolon 30 mg 1-mal täglich über 5 Tage und Benralizumab 100 mg 1-mal subkutan injiziert (BENRA-plus-PRED-Gruppe), Placebo-Tabletten 1-mal täglich über 5 Tage und Benralizumab 100 mg 1-mal subkutan injiziert (BENRA-Gruppe) bzw. Prednisolon 30 mg 1-mal täglich über 5 Tage und Placebo 1-mal subkutan injiziert (PRED-Gruppe). Die Randomisierung erfolgte über ein zentralisiertes, interaktives computergesteuertes Randomisierungssystem. Alle Patienten und das an der Datenerhebung beteiligte Studienpersonal waren gegenüber den Ergebnissen der Blutuntersuchungen und der Behandlungszuweisung verblindet. Die koprimären Endpunkte waren der Anteil der Patienten mit Therapieversagen nach 90 Tagen und die Gesamtsymptomatik auf der visuellen Analogskala (VAS) an Tag 28 in den gepoolten Benralizumab-Gruppen im Vergleich zur Prednisolon-Gruppe allein und wurden in der Intention-to-treat-Population analysiert. Die Studie wurde auf clinicaltrials.gov unter der Nummer NCT04098718 registriert. Ergebnisse: Zwischen dem 13. Mai 2021 und dem 5. Februar 2024 wurden 287 Patienten für die Aufnahme in die Studie gescreent. 129 Patienten wurden ausgeschlossen, da keine Exazerbation vorlag oder die Ausschlusskriterien für Eosinophilie nicht erfüllt waren. 158 Patienten mit einer akuten eosinophilen Exazerbation von Asthma oder COPD wurden randomisiert, 86 (54%) waren weiblich und 72 (46%) männlich, mit einem Durchschnittsalter von 57 (18–84) Jahren. 53 Patienten wurden in die PRED-Gruppe, 53 in die BENRA-Gruppe und 52 in die BENRA-plus-PRED-Gruppe randomisiert. Nach 90 Tagen brachen 39 (74%) von 53 Patienten in der PRED-Gruppe und 47 (45%) von 105 Patienten in der gepoolten BENRA-Gruppe die Behandlung ab (OR 0,26; 95%-KI 0,13–0,56; p = 0,0005). Die mittlere Differenz in der 28-Tage-Gesamt-VAS betrug 49 mm (95%-KI 14–84; p = 0,0065) zugunsten der gepoolten BENRA-Gruppe. Es gab keine tödlichen Nebenwirkungen und Benralizumab wurde gut vertragen. Bemerkenswert ist, dass die unerwünschten Ereignisse Hyperglykämie und Sinusitis bzw. Sinusinfektion nur mit der Studienmedikation Prednisolon assoziiert waren. Schlussfolgerung: Benralizumab kann zur Behandlung akuter eosinophiler Exazerbationen eingesetzt werden und erzielt bessere Ergebnisse als die derzeitige Standardtherapie mit Prednisolon allein. Diese Ergebnisse bieten eine neue Option für die Behandlung von eosinophilen Endotypen bei Asthma- und COPD-Exazerbationen. Finanzierung: AstraZeneca.

Bordag N.