Respiratory Research最新文献

Background: In recent years, the importance of sex as a factor influencing medical care has received increasing attention in the field of intensive care medicine. The objective of this study was to examine the influence of sex in prolonged weaning.

Methods: A retrospective analysis of patients undergoing prolonged weaning at Thoraxklinik, University Hospital Heidelberg between 12/08 and 12/23 was conducted. Patients with neuromuscular diseases were excluded from the analyses. The risk factors for weaning failure in men and women were identified through stepwise cox-regression analyses.

Results: A total of 785 patients were included, of whom 313 (39.9%) were women. 77.9% of the women and 75.4% of the men were successfully weaned from invasive ventilation. In group comparisons and multivariable analyses, sex was not found to be a risk factor for weaning failure. Cox regression analyses were performed separately for both sexes on the outcome of weaning failure, adjusting for relevant covariates. The results indicated that age ≥ 65 years (HR 2.38, p < 0.001) and the duration of IMV before transfer to the weaning centre (HR 1.01/day, p < 0.001) were independent risk factors in men. In women, however, the duration of IMV before transfer (HR 1.01, p < 0.001), previous non-invasive ventilation (HR 2.9, p 0.005), the presence of critical illness polyneuropathy (HR 1.82; p = 0.040) and delirium (HR 2.50, p = 0.017) were identified as relevant risk factors. In contrast delirium was associated with a favourable weaning outcome in men (HR 0.38, p = 0.020) and nosocomial pneumonia as a reason for prolonged weaning in women (HR 0.43; p = 0.032).

Conclusion: The analyses indicate that there are sex-based differences in the risk factors associated with weaning failure. Further studies, ideally prospective, should confirm these findings to assess whether sex is a factor that should be taken into account to improve weaning outcomes.

Introduction: The usual interstitial pneumonia (UIP) pattern, hallmark of idiopathic pulmonary fibrosis (IPF), may induce harmful local overdistension during mechanical ventilation given the juxtaposition of different tissue elasticities. Mechanotransduction, linking mechanical stress and strain to molecular pro-fibrotic pathways, likely contributes to fibrosis progression. Understanding the mechanical forces and aeration patterns in the lungs of IPF patients is crucial for unraveling potential mechanisms of disease progression. Quantitative lung computed tomography (CT) can accurately assess the air content of lung regions, thus informing on zonal distension. This study aims to investigate radiological evidence of lung over aeration in spontaneously breathing UIP patients compared to healthy controls during maximal inspiration.

Methods: Patients with IPF diagnosis referred to the Center for Rare Lung Diseases of the University Hospital of Modena (Italy) in the period 2020-2023 who underwent High Resolution Computed Tomography (HRCT) scans at residual volume (RV) and total lung capacity (TLC) using standardized protocols were retrospectively considered eligible. Patients with no signs of lung disease at HRCT performed with the same image acquisition protocol nor at pulmonary function test (PFTs) served as controls. Lung segmentation and quantitative analysis were performed using 3D Slicer software. Lung volumes were measured, and specific density thresholds defined over aerated and fibrotic regions. Comparison between over aerated lung at RV and TLC in the two groups and according to lung lobes was sought. Further, the correlation between aerated lung and the extent of fibrosis was assessed and compared at RV and TLC.

Results: IPF patients (N = 20) exhibited higher over aerated lung proportions than controls (N = 15) both at RV and TLC (4.5% vs. 0.7%, p < 0.0001 and 13.8% vs. 7%, p < 0.0001 respectively). Over aeration increased significantly from RV to TLC in both groups, with no intergroup difference (p = 0.67). Sensitivity analysis revealed significant variations in over aerated lung areas among lobes when passing from RV to TLC with no difference within lobes (p = 0.28). Correlation between over aeration and fibrosis extent was moderate at RV (r = 0.62, p < 0.0001) and weak at TLC (r = 0.27, p = 0.01), being the two significantly different at interpolation analysis (p < 0.0001).

Conclusions: This study provides the first evidence of radiological signs of lung over aeration in patients with UIP-pattern patients when passing from RV to TLC. These findings offer new insights into the complex interplay between mechanical forces, lung structure, and fibrosis and warrant larger and longitudinal investigations.

Background and aims: Because bronchoscopy is an invasive procedure, sedatives and analgesics are commonly administered, which may suppress the patient's spontaneous breathing and can lead to hypoventilation and hypoxemia. Few reports exist on the dynamic monitoring of oxygenation and ventilation during bronchoscopy. This study aimed to prospectively monitor and evaluate oxygenation and ventilation during bronchoscopy using transcutaneous arterial blood oxygen saturation and carbon dioxide.

Methods: We included patients who required pathological diagnosis using fluoroscopic bronchoscopy at our hospital between March 2021 and April 2022. Midazolam was intravenously administered to all patients as a sedative during bronchoscopy, and fentanyl was administered in addition to midazolam when necessary. A transcutaneous blood gas monitor was used to measure dynamic changes, including arterial blood partial pressure of carbon dioxide (tcPCO₂), transcutaneous arterial blood oxygen saturation (SpO₂), pulse rate, and perfusion index during bronchoscopy. Quantitative data of tcPCO₂ and SpO₂ were presented as mean ± standard deviation (SD) (min-max), while the quantitative data of midazolam plus fentanyl and midazolam alone were compared. Similarly, data on sex, smoking history, and body mass index were compared. Subgroup comparisons of the difference (Δ value) between baseline tcPCO₂ at the beginning of bronchoscopy and the maximum value of tcPCO₂ during the examination were performed.

Results: Of the 117 included cases, consecutive measurements were performed in 113 cases, with a success rate of 96.6%. Transbronchial lung biopsy was performed in 100 cases, whereas transbronchial lung cryobiopsy was performed in 17 cases. Midazolam and fentanyl were used as anesthetics during bronchoscopy in 46 cases, whereas midazolam alone was used in 67 cases. The median Δ value in the midazolam plus fentanyl and midazolam alone groups was 8.10 and 4.00 mmHg, respectively, indicating a significant difference of p < 0.005. The mean ± standard deviation of tcPCO₂ in the midazolam plus fentanyl and midazolam alone groups was 44.8 ± 7.83 and 40.6 ± 4.10 mmHg, respectively. The SpO₂ in the midazolam plus fentanyl and midazolam alone groups was 94.4 ± 3.37 and 96.2 ± 2.61%, respectively, with a larger SD and greater variability in the midazolam plus fentanyl group.

Conclusion: A transcutaneous blood gas monitor is non-invasive and can easily measure the dynamic transition of CO₂. Furthermore, tcPCO₂ can be used to evaluate the ventilatory status during bronchoscopy easily. A transcutaneous blood gas monitor may be useful to observe regarding respiratory depression during bronchoscopy, particularly when analgesics are used.

Background: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited.

Methods: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU.

Results: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05).

Conclusion: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

Background: The prevalence of non-small cell lung cancer (NSCLC) is notably elevated in individuals diagnosed with idiopathic pulmonary fibrosis (IPF). Secreted phosphoprotein 1 (SPP1), known for its involvement in diverse physiological processes, including oncogenesis and organ fibrosis, has an ambiguous role at the intersection of IPF and NSCLC. Our study sought to elucidate the function of SPP1 within the pathogenesis of IPF and its subsequent impact on NSCLC progression.

Methods: Four GEO datasets was analyzed for common differential genes and TCGA database was used to analyze the prognosis. The immune infiltration was analyzed by TIMER database. SPP1 expression was examined in human lung tissues, the IPF fibroblasts and the BLM-induced mouse lung fibrosis model. Combined with SPP1 gene gain- and loss-of-function, qRT-PCR, Western blot, EdU and CCK-8 experiments were performed to evaluate the effects and mechanisms of SPP1 in IPF progression. Effect of SPP1 on NSCLC was detected by co-cultured IPF fibroblasts and NSCLC cells.

Results: Through bioinformatics analysis, we observed a significant overexpression of SPP1 in both IPF and NSCLC patient datasets, correlating with enhanced immune infiltration of cancer-associated fibroblasts in NSCLC. Elevated levels of SPP1 were detected in lung tissue samples from IPF patients and bleomycin-induced mouse models, with partial colocalization observed with α-smooth muscle actin. Knockdown of SPP1 inhibits TGF-β1-induced differentiation of fibroblasts to myofibroblasts and the proliferation of IPF fibroblasts. Conversely, SPP1 overexpression promoted IPF fibroblast proliferation via PI3K/Akt/mTOR pathway. Furthermore, IPF fibroblasts promoted NSCLC cell proliferation and activated the PI3K/Akt/mTOR pathway; these effects were attenuated by SPP1 knockdown in IPF fibroblasts.

Conclusions: Our findings suggest that SPP1 functions as a molecule promoting both fibrosis and tumorigenesis, positioning it as a prospective therapeutic target for managing the co-occurrence of IPF and NSCLC.

Background: Expiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI).

Methods: A retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance.

Results: The mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment.

Conclusions: COPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.

Background: Subject-ventilator asynchrony (SVA) was shown to be associated with negative clinical outcomes. To elucidate pathophysiology pathways and effects of SVA on lung tissue histology a reproducible animal model of artificially induced asynchrony was developed and evaluated.

Methods: Alterations in ventilator parameters were used to induce the three main types of asynchrony: ineffective efforts (IE), auto-triggering (AT), and double-triggering (DT). Airway flow and pressure, as well as oesophageal pressure waveforms, were recorded, asynchrony cycles were manually classified and the asynchrony index (AIX) was calculated. Bench tests were conducted on an active lung simulator with ventilator settings altered cycle by cycle. The developed algorithm was evaluated in three pilot experiments and a study in pigs ventilated for twelve hours with AIX = 25%.

Results: IE and AT were induced reliably and fail-safe by end-expiratory hold and adjustment of respiratory rate, respectively. DT was provoked using airway pressure ramp prolongation, however not controlled specifically in the pilots. In the subsequent study, an AIX = 28.8% [24.0%-34.4%] was induced and maintained over twelve hours.

Conclusions: The method allows to reproducibly induce and maintain three clinically relevant types of SVA observed in ventilated patients and may thus serve as a useful tool for future investigations on cellular and inflammatory effects of asynchrony.

Introduction: Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension.

Methods: RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis.

Results: CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic.

Conclusion: Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.

Background: Accurate prediction of short-term mortality in acute pulmonary embolism (APE) is very important. The aim of the present study was to analyze the prognostic role of radiomics values of epicardial adipose tissue (EAT) in APE.

Methods: Overall, 508 patients were included into the study, 209 female (42.1%), mean age, 64.7 ± 14.8 years. 4.6%and 12.4% died (7- and 30-day mortality, respectively). For external validation, a cohort of 186 patients was further analysed. 20.2% and 27.7% died (7- and 30-day mortality, respectively). CTPA was performed at admission for every patient before any previous treatment on multi-slice CT scanners. A trained radiologist, blinded to patient outcomes, semiautomatically segmented the EAT on a dedicated workstation using ImageJ software. Extraction of radiomic features was applied using the pyradiomics library. After correction for correlation among features and feature cleansing by random forest and feature ranking, we implemented feature signatures using 247 features of each patient. In total, 26 feature combinations with different feature class combinations were identified. Patients were randomly assigned to a training and a validation cohort with a ratio of 7:3. We characterized two models (30-day and 7-day mortality). The models incorporate a combination of 13 features of seven different image feature classes.

Findings: We fitted the characterized models to a validation cohort (n = 169) in order to test accuracy of our models. We observed an AUC of 0.776 (CI 0.671-0.881) and an AUC of 0.724 (CI 0.628-0.820) for the prediction of 30-day mortality and 7-day mortality, respectively. The overall percentage of correct prediction in this regard was 88% and 79% in the validation cohorts. Lastly, the AUC in an independent external validation cohort was 0.721 (CI 0.633-0.808) and 0.750 (CI 0.657-0.842), respectively.

Interpretation: Radiomics parameters of EAT are strongly associated with mortality in patients with APE.

Clinical trial number: Not applicable.

Background: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has expanded considerably, though evidence-based selection criteria and long-term outcome data are lacking. The purpose of this study was to evaluate whether risk factors often used to exclude patients from ECMO BTT-specifically older age and not yet being listed for transplant-are validated by long-term outcomes.

Methods: To ensure minimum 5-year follow-up, a retrospective cohort study was performed of adult patients actively listed for lung transplantation at a high-volume center and bridged on ECMO between January 2012 and December 2017. Data was collected through January 1, 2023.

Results: Among 50 patients bridged on ECMO, 25 survived to transplant. Median age at listing was 58 (interquartile range [IQR], 42-65) in the transplanted group and 65 (IQR, 56.5-69) in the deceased group (P = 0.051). One-year, 3-year, and 5-year survival were 88% (22/25), 60% (15/25), and 44% (11/25), respectively, with eight patients still living at the time of review. Median time spent at home during the year post-transplant was 340 days (IQR, 314-355). Older age at listing was a negative predictor of survival on ECMO to transplant (odds ratio 0.92 [95% confidence interval, 0.86-0.99], P = 0.01). Thirteen patients were placed on ECMO prior to being listed and three were listed the same day as ECMO cannulation, with 10/16 transplanted. No significant difference in post-transplant survival was found between patients placed on ECMO prior to listing (n = 10) and those already listed (n = 15) (P = 0.93, log-rank). Serial post-transplant spirometry up to 5 years and surveillance transbronchial biopsy demonstrated good allograft function and low rates of cellular rejection.

Conclusions: In one of the oldest cohorts of ECMO BTT patients described, favorable survival outcomes and allograft function were observed up to 5 years irrespective of whether patients were previously listed or bridged to decision. Despite inherent limitations to this retrospective, single-center study, the data presented support the feasibility of ECMO BTT in older and not previously listed advanced lung disease patients.