Since critical respiratory muscle workload is a significant determinant of weaning failure, applied mechanical power (MP) during artificial ventilation may serve for readiness testing before ...proceeding on a spontaneous breathing trial (SBT). Secondary analysis of a prospective, observational study in 130 prolonged ventilated, tracheotomized patients. Calculated MP's predictive SBT outcome performance was determined using the area under receiver operating characteristic curve (AUROC), measures derived from k-fold cross-validation (likelihood ratios, Matthew's correlation coefficient MCC), and a multivariable binary logistic regression model. Thirty (23.1%) patients failed the SBT, with absolute MP presenting poor discriminatory ability (MCC 0.26; AUROC 0.68, 95%CI 0.59‒0.75, p = 0.002), considerably improved when normalized to lung-thorax compliance (LTC
-MP, MCC 0.37; AUROC 0.76, 95%CI 0.68‒0.83, p < 0.001) and mechanical ventilation P
CO
(so-called power index of the respiratory system PI
: MCC 0.42; AUROC 0.81 0.73‒0.87, p < 0.001). In the logistic regression analysis, PI
(OR 1.48 per 1000 cmH
O
/min, 95%CI 1.24‒1.76, p < 0.001) and its components LTC
-MP (1.25 per 1000 cmH
O
/min, 1.06‒1.46, p < 0.001) and mechanical ventilation P
CO
(1.17 1.06‒1.28, p < 0.001) were independently related to SBT failure. MP normalized to respiratory system compliance may help identify prolonged mechanically ventilated patients ready for spontaneous breathing.
Systemic anticancer therapies (SACTs) are the leading cause of drug-induced interstitial lung disease (ILD). As more novel SACTs become approved, the incidence of this potentially life-threatening ...adverse event (AE) may increase. Early detection of SACT-related ILD allows for prompt implementation of drug-specific management recommendations, improving the likelihood of AE resolution and, in some instances, widening the patient’s eligibility for future cancer treatment options. ILD requires a diagnosis of exclusion through collaboration with the patient’s multidisciplinary team to rule out other possible etiologies of new or worsening respiratory signs and symptoms. At Grade 1, ILD is asymptomatic, and thus the radiologist is key to detecting the AE prior to the disease severity worsening. Planned computed tomography scans should be reviewed for the presence of ILD in addition to being assessed for tumor response to treatment, and when ILD is suspected, a high-resolution computed tomography (HRCT) scan should be requested immediately. An HRCT scan, with < 2-mm slice thickness, is the most appropriate method for detecting ILD. Multiple patterns of ILD exist, which can impact patient prognosis. The four main patterns include acute interstitial pneumonia / acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, and non-specific interstitial pneumonia; their distinct radiological features, along with rarer patterns, are discussed here. Furthermore, HRCT is essential for following the course of ILD and might help to determine the intensity of AE management and the appropriateness of re-challenging with SACT, where indicated by drug-specific prescribing information. ILD events should be monitored closely until complete resolution.
Critical relevance statement
The incidence of potentially treatment-limiting and life-threatening systemic anticancer therapy-related interstitial lung disease (SACT-related ILD) events is likely increasing as more novel regimens become approved. This review provides best-practice recommendations for the early detection of SACT-related ILD by radiologists.
Key Points
Radiologists are crucial in detecting asymptomatic (Grade 1) ILD before severity/prognosis worsens.
High-resolution computed tomography is the most appropriate method for detecting ILD.
Drug-induced ILD is a diagnosis of exclusion, involving a multidisciplinary team.
Familiarity with common HRCT patterns, described here, is key for prompt detection.
Physicians should highlight systemic anticancer therapies (SACTs) with a known risk for interstitial lung diseases (ILD) on scan requisitions.
Graphical Abstract
Due to immunosuppression, transplant recipients are at higher risk of infections with SARS-CoV-2 and worse clinical outcomes than immunocompetent hosts. Furthermore, lung transplant patients ...represent a special group among solid organ recipients, since pneumonia is the main manifestation of COVID-19. However, data on the course of disease and the changes in morbidity and mortality during the course of the pandemic are limited. In our pulmonary rehabilitation clinic, we treat patients shortly after lung transplant as well as long-term transplant patients. Over the last almost 4 years of pandemic, we witnessed several COVID-19 infections in lung transplant patients in our clinic as well as patients who acquired an infection beforehand. In this paper, we aim at retrospectively describing a series of recent COVID-19 cases in our clinic, looking at the clinical course of disease and outcomes in lung transplant patients.
Background Careful patient selection is the prerequisite to raise transplant benefit. In lung transplant (LT) candidates, the effect of body mass index (BMI) on postoperative outcome remains ...controversial, possibly due to the inaccuracy of BMI in discriminating between fat and muscle mass. We therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by BMI regarding postoperative outcome. Methods All LT recipients from 2011 to 2014 were included and retrospectively analyzed. Lean psoas area (LPA) was assessed from pretransplant computed tomography scans, and associations with postoperative outcomes were investigated. Results Included were 103 consecutive LT recipients with a mean pre-LT BMI of 22.0 ± 4.0 kg/m2 and a mean LPA of 22.3 ± 8.3 cm2 . LPA was inversely associated with length of mechanical ventilation ( p = 0.03), requirement of tracheostomy ( p = 0.035), and length of stay in the intensive care unit ( p = 0.02), while controlling for underlying disease, BMI, sex, age, and procedure; in contrast, BMI was not ( p = 0.25, p = 0.54, and p = 0.42, respectively.). Multiple regression analysis revealed that the 6-minute walk distance at the end of pulmonary rehabilitation was significantly associated with LPA ( p = 0.02). Conclusions LPA can easily be assessed in LT candidates as part of pretransplant evaluation and was significantly associated with short-term outcome, whereas BMI was not. Assessment of LPA may provide additional information on body composition beyond BMI. However, the clinical utility has to be further evaluated.
Various complications may arise from prolonged mechanical ventilation, but the risk of tracheal stenosis occurring late after translaryngeal intubation or tracheostomy is less common. This study ...aimed to determine the prevalence, type, risk factors, and management of tracheal stenoses in mechanically ventilated tracheotomized patients deemed ready for decannulation following prolonged weaning.
A retrospective observational study on 357 prolonged mechanically ventilated, tracheotomized patients admitted to a specialized weaning center over seven years. Flexible bronchoscopy was used to discern the type, level, and severity of tracheal stenosis in each case. We described the management of these stenoses and used a binary logistic regression analysis to determine independent risk factors for stenosis development.
On admission, 272 patients (76%) had percutaneous tracheostomies, and 114 patients (32%) presented mild to moderate tracheal stenosis following weaning completion, with a median tracheal cross-section reduction of 40% (IQR 25-50). The majority of stenoses (88%) were located in the upper tracheal region, most commonly resulting from localized granulation tissue formation at the site of the internal stoma (96%). The logistic regression analysis determined that obesity (OR 2.16 95%CI 1.29-3.63, P < 0.01), presence of a percutaneous tracheostomy (2.02 1.12-3.66, P = 0.020), and cricothyrotomy status (5.35 1.96-14.6, P < 0.01) were independently related to stenoses. Interventional bronchoscopy with Nd:YAG photocoagulation was a highly effective first-line treatment, with only three patients (2.6%) ultimately referred to tracheal surgery.
Tracheal stenosis is commonly observed among prolonged ventilated patients with tracheostomies, characterized by localized hypergranulation and mild to moderate airway obstruction, with interventional bronchoscopy providing satisfactory results.
Recently two novel drugs, pirfenidone and nintedanib have been licenced for the treatment of idiopathic pulmonary fibrosis (IPF), marking a turning point in this previously untreatable, fatal disease.
Bronchiolitis obliterans syndrome (BOS) is a major complication after lung transplantation (LTx). BOS is characterised by massive peribronchial fibrosis, leading to air trapping-induced pulmonary ...dysfunction. Cathepsin B, a lysosomal cysteine protease, has been shown to enforce fibrotic pathways in several diseases. However, the relevance of cathepsin B in BOS progression has not yet been addressed. The aim of the study was to elucidate the function of cathepsin B in BOS pathogenesis.We determined cathepsin B levels in bronchoalveolar lavage fluid (BALF) and lung tissue from healthy donors (HD) and BOS LTx patients. Cathepsin B activity was assessed
a fluorescence resonance energy transfer-based assay and protein expression was determined using Western blotting, ELISA and immunostaining. To investigate the impact of cathepsin B in the pathophysiology of BOS, we used an
orthotopic left LTx mouse model. Mechanistic studies were performed
using macrophage and fibroblast cell lines.We found a significant increase of cathepsin B activity in BALF and lung tissue from BOS patients, as well as in our murine model of lymphocytic bronchiolitis. Moreover, cathepsin B activity was associated with increased biosynthesis of collagen and had a negative effect on lung function. We observed that cathepsin B was mainly expressed in macrophages that infiltrated areas characterised by a massive accumulation of collagen deposition. Mechanistically, macrophage-derived cathepsin B contributed to transforming growth factor-β1-dependent activation of fibroblasts, and its inhibition reversed the phenotype.Infiltrating macrophages release active cathepsin B, thereby promoting fibroblast activation and subsequent collagen deposition, which drive BOS. Cathepsin B represents a promising therapeutic target to prevent the progression of BOS.
The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single‐cell transcriptomic and proteomic data from ...multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single‐cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulatory factor CFHR1. We further discovered CRTAC1 as a biomarker of alveolar type‐2 epithelial cell health status in lavage fluid and plasma. Using cross‐modal analysis and machine learning, we identified the cellular source of biomarkers and demonstrated that information transfer between modalities correctly predicts disease status, suggesting feasibility of clinical cell state monitoring through longitudinal sampling of body fluid proteomes.
Synopsis
Multi‐modal integration of single‐cell RNA‐seq data from lung tissue and proteomic data from body fluids across independent lung fibrosis patient cohorts revealed biomarker signatures that correspond with cell state changes during disease progression.
Changes in gene expression and cell type frequency are reproducible across cohorts.
Protein biomarker signatures of lung function decline in pulmonary fibrosis.
Multi‐modal data transfer identifies cellular source of regulated proteins.
An activated pericyte state features inflammatory and complement regulators.
CRTAC1 levels in body fluids indicate AT2 cell dedifferentiation in disease.
Multi‐modal integration of single‐cell RNA‐seq data from lung tissue and proteomic data from body fluids across independent lung fibrosis patient cohorts revealed biomarker signatures that correspond with cell state changes during disease progression.
Abstract A prospective observational study comparing mechanical power density (MP normalized to dynamic compliance) with traditional spontaneous breathing indexes (e.g., predicted body weight ...normalized tidal volume VT/PBW, rapid shallow breathing index RSBI, or the integrative weaning index IWI) for predicting prolonged weaning failure in 140 tracheotomized patients. We assessed the diagnostic accuracy of these indexes at the start and end of the weaning procedure using ROC curve analysis, expressed as the area under the receiver operating characteristic curve (AUROC). Weaning failure occurred in 41 out of 140 patients (29%), demonstrating significantly higher MP density (6156 cmH 2 O 2 /min 4402–7910 vs. 3004 cmH 2 O 2 /min 2153–3917, P < 0.01), lower spontaneous VT/PBW (5.8 mL*kg −1 4.8–6.8 vs. 6.6 mL*kg −1 5.7–7.9, P < 0.01) higher RSBI (68 min −1 *L −1 44–91 vs. 55 min −1 *L −1 41–76, P < 0.01) and lower IWI (41 L 2 /cmH 2 O*%*min*10 −3 25–72 vs. 71 L 2 /cmH 2 O*%*min*10 -3 50–106, P < 0.01) and at the end of weaning. MP density was more accurate at predicting weaning failures (AUROC 0.91 95%CI 0.84–0.95) than VT/PBW (0.67 0.58–0.74), RSBI (0.62 0.53–0.70), or IWI (0.73 0.65–0.80), and may help clinicians in identifying patients at high risk for long-term ventilator dependency.
Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ...ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman’s coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman’s
ρ
= 0.252 95% CI 0.129–0.369,
p
< 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation (
ρ
= 0.452 0.345–0.548,
p
< 0.01) and enhancing PMV prediction (AUROC 0.78 95% CI 0.72–0.83,
p
< 0.01) compared to MP (AUROC 0.66 0.60–0.72,
p
< 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation.
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