Daily Respiratory Research Analysis

RATIONALE: Despite significant advances in patient care and outcomes, criteria for cardiopulmonary exercise testing (CPET) in risk stratification guidelines for lung resection have not been updated in over a decade. We hypothesised that CPET no longer holds additional predictive value for postoperative complications. METHODS: In this secondary analysis, we included lung resection candidates from two prospective, multicentre studies eligible for CPET and assessed with preoperative pulmonary function tests (PFTs) and arterial blood gas analysis. Postoperative pulmonary (PPCs) and cardiovascular complications (PCCs) were documented during hospitalisation. We trained five types of machine learning models applying nested cross-validation to predict complications and compared predictive performance based on four metrics, including area under the receiver operating characteristic curve (AUC-ROC). RESULTS: A total of 497 patients were included. PPCs developed in 71 (14%) patients. Adding CPET parameters to PFTs and baseline clinical data did not improve the ability of models to predict PPCs in unselected patients (AUC-ROC=0.72-0.78; p=0.47), nor in those meeting American College of Chest Physicians (ACCPs) (n=236; AUC-ROC=0.64-0.78; p=0.70) or European Respiratory Society/European Society of Thoracic Surgery (ERS/ESTS) criteria (n=168; AUC-ROC=0.59-0.76; p=0.92). PCCs developed in 90 (18%) patients. CPET parameters likewise did not improve model performance for the prediction of PCCs in unselected patients (AUC-ROC=0.65-0.73; p=0.96), nor in the ACCP (AUC-ROC=0.61-0.73; p=0.82) or ERS/ESTS subgroups (AUC-ROC=0.62-0.69; p=0.87). CONCLUSIONS: In contemporary surgical practice, CPET did not improve the predictive performance of machine learning models for PPCs or PCCs in patients with an indication based on established guidelines or in those without. The role of CPET in preoperative risk stratification for lung resection should be re-evaluated. TRIAL REGISTRATION NUMBER: NCT03498352, NCT04826575.

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period. METHODS: This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching. FINDINGS: We identified 407 300 (87·5%) of 465 717 eligible children and adolescents with a first infection episode and 58 417 (12·5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233 842 (50·2%) patients were male and 231 875 (49·8%) were female. The mean age was 8·17 years (SD 6·58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903·7 (95% CI 780·9-1026·5) in the first infection group and 1883·7 (1565·1-2202·3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2·08 [1·68-2·59]) and a range of symptoms and conditions potentially related to PASC (RR range 1·15-3·60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms. INTERPRETATION: Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies. FUNDING: National Institutes of Health.

BACKGROUND: The relationship between microbiota and the gut-lung axis has been extensively studied in both experimental and epidemiological contexts. However, it is still unclear whether the gut microbiome plays a causal role in the development of pneumonia. METHODS: Our study initially identified the genetic instruments in the gut microbiota GWAS across phylum, class, order, family, and genus levels. Pneumonia data were sourced from the open GWAS project of the Integrated Epidemiology Group (IEU). Mendelian randomization (MR) analysis employed several methods such as inverse variance weighting (IVW), weighted median, and MR-Egger, with Cochran's Q were calculated to assess heterogeneity via IVW and MR-Egger. Additionally, MR-PRESSO and MR-Egger intercepts were utilized to mitigate horizontal pleiotropy. A retrospective case-control study collected anal swab samples from severe pneumonia patients on the 1st and 3rd days after ICU admission. Samples were analyzed using 16S ribosomal ribonucleic acid (16S rRNA) and PERMANOVA analysis. RESULTS: Eleven potential causal relationships between the gut microbiome and pneumonia (critical care), as well as nine potential causal relationships between the gut microbiome and pneumonia (28-day death in critical care) were identified. By integrating the results of PERMANOVA analysis with Mendelian randomization analysis, we were able to determine a negative correlation between genus Akkermansia and lactate levels, as well as length of ICU days in patients with septic acute respiratory distress syndrome (ARDS). Moreover, we found a potential negative causal relationship between the genus Akkermansia and pneumonia (28-day death in critical care) (OR 0.42, 95% CI 0.22-0.79, P = 0.007). CONCLUSIONS: Our Mendelian randomization analysis has provided evidence for a potential causal relationship between gut microbiota and pneumonia. Furthermore, we observed that the genus Akkermansia may decrease the risk of pneumonia (28-day death in critical care), as observed in septic ARDS patients which Akkermansia could reduce ICU days and lactate levels. These findings provide valuable insights into the gut-lung axis and have the latent to inform future research in this field. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/index.html , ChiCTR2300075450).