Murine orthotopic lung transplant models: A comprehensive overview of genetic mismatch degrees and histopathological insights into chronic lung allograft dysfunction.

Currently, lung transplantation outcome remains inferior compared to other solid organ transplantations. A major cause for limited survival after lung transplantation is chronic lung allograft dysfunction. Numerous animal models have been developed to investigate chronic lung allograft dysfunction to discover adequate treatments. The murine orthotopic lung transplant model has been further optimized over the last years. However, different degrees of genetic mismatch between donor and recipient mice have been used, applying a single, minor, moderate, and major genetic mismatch. This review aims to reassess the existing murine mismatch models and provide a comprehensive overview, with a specific focus on their eventual histopathological presentation. This will be crucial to leverage this model and tailor it according to specific research needs.

Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial.

BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037. CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.

COVID-19 in three waves in a tertiary referral hospital in Belgium: a comparison of patient characteristics, management, and outcome.

PURPOSE: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021. METHODS: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression. RESULTS: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality. CONCLUSIONS: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution.

Evaluation of the learning effect on the 6-min walk distance in adults with long COVID.

There was no learning effect found on 6-min walk distance (6MWD) in patients with long COVID, performing a 6-min walk test twice. However, considerable variation in the difference between the two 6MWDs was observed: only 51% showed an increase. https://bit.ly/3H70G1r.

Changes in Control Status of COPD Over Time and Their Consequences: A Prospective International Study / Cambios en el estado de control de la EPOC a lo largo del tiempo y sus consecuencias: un estudio internacional prospectivo

INTRODUCTION: Control status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time. METHOD: Prospective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up. RESULTS: A total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV1(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47-4.69) and OR = 4.25 (95%CI 2.48-7.27) for hospitalization compared with a controlled patient visit. CONCLUSIONS: Evaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status

INTRODUCCIÓN: El estado de control de la enfermedad puede ser una herramienta útil para evaluar la respuesta al tratamiento de la EPOC en cada asistencia a consulta. El estado de control de la enfermedad ha demostrado tener valor predictivo a largo plazo para las exacerbaciones, pero no existe información sobre el valor predictivo a corto plazo de la falta de control de la EPOC y los cambios en dicho control a lo largo del tiempo. MÉTODO: Estudio prospectivo, internacional, multicéntrico enfocado en describir el valor pronóstico a corto plazo (6 meses) del estado de control de la enfermedad en pacientes con EPOC. Los pacientes con EPOC se clasificaron como con enfermedad controlada/sin controlar al inicio del estudio y en las 3 visitas de seguimiento separadas 6 meses, utilizando criterios de control previamente validados. Se compararon las tasas de exacerbación moderada y grave entre visitas en las que la enfermedad estaba controlada y aquellas en las que no y entre pacientes con control persistente de la enfermedad, pacientes sin control de la enfermedad y aquellos cuyo estado de control cambió durante el seguimiento. RESULTADOS: Se analizó a un total de 267 pacientes: 80 (29,8%) presentaron control persistente de la enfermedad, 43 (16%) permanecieron con enfermedad no controlada de manera persistente y 144 (53,7%) presentaron un cambio en el estado de control de su EPOC durante el seguimiento. Los pacientes con control persistente de su enfermedad fueron con mayor frecuencia hombres, con un índice de masa corporal más bajo (no elevado) y un FEV1 (%) más alto. Durante los 6 meses posteriores a una visita en la que la enfermedad del paciente no estaba controlada, la odds ratio (OR) para presentar una exacerbación moderada fue de 3,41 (intervalo de confianza [IC] del 95%: 2,47 a 4,69) y la OR = 4,25 (IC del 95%: 2,48 a 7,27) para la hospitalización, en comparación con una visita en la que la EPOC estaba controlada. CONCLUSIONES: La evaluación del estado de control de la EPOC en cada asistencia a consulta proporciona información pronóstica relevante sobre el riesgo de exacerbación en los próximos 6 meses. La falta de control es una señal de alarma que debe motivar la investigación y la acción para lograr el control de la enfermedad