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result(s) for
"Kneidinger, Nikolaus"
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Mechanical power normalized to lung-thorax compliance indicates weaning readiness in prolonged ventilated patients
2022
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
dyn
-MP, MCC 0.37; AUROC 0.76, 95%CI [0.68‒0.83],
p
< 0.001) and mechanical ventilation P
a
CO
2
(so-called power index of the respiratory system [PI
rs
]: MCC 0.42; AUROC 0.81 [0.73‒0.87],
p
< 0.001). In the logistic regression analysis, PI
rs
(OR 1.48 per 1000 cmH
2
O
2
/min, 95%CI [1.24‒1.76],
p
< 0.001) and its components LTC
dyn
-MP (1.25 per 1000 cmH
2
O
2
/min, [1.06‒1.46],
p
< 0.001) and mechanical ventilation P
a
CO
2
(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.
Journal Article
Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity
by
Mümmler Carlo
,
Barton, Jürgen
,
Hellmuth, Johannes C
in
Abnormalities
,
Antibodies
,
Asymptomatic
2022
ObjectiveEvaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors.MethodsPatients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4 months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function.Results76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate–severe disease. After 4 months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p < 0.001). Further risk factors for DLCO impairment were COPD (p < 0.001), SARS-CoV-2 antibody-Titer (p = 0.014) and in hospitalized patients CT score. A decrease of paO2 > 3 mmHg during cycle exercise occurred in 1/5 of patients after mild disease course.ConclusionWe characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition.
Journal Article
Tracheal stenosis in prolonged mechanically ventilated patients: prevalence, risk factors, and bronchoscopic management
by
Paderewska, Joanna
,
Ghiani, Alessandro
,
Munker, Dieter
in
Aged
,
Airway management
,
Artificial respiration
2022
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Journal Article
The radiologist’s role in detecting systemic anticancer therapy-related interstitial lung disease: an educational review
by
Kneidinger, Nikolaus
,
Dinkel, Julien
,
Tarantino, Paolo
in
Asymptomatic
,
Cancer
,
Computed tomography
2024
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 statementThe 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 PointsRadiologists 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.
Journal Article
COVID-19 in Lung Transplant Recipients: A Report on 10 Recent Cases
2024
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.
Journal Article
Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers
2021
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.
Graphical Abstract
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.
Journal Article
Mechanical Power Density Predicts Prolonged Ventilation Following Double Lung Transplantation
2023
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.
Journal Article
Mechanical power density, spontaneous breathing indexes, and prolonged weaning failure: a prospective cohort study
2024
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.
Journal Article
Proposal of a radiation-free screening protocol for early detection of interstitial lung involvement in seropositive and ACPA-positive rheumatoid arthritis
by
Hoffmann, Martin
,
von Wulffen, Werner
,
Welcker, Martin
in
Aged
,
Anaerobic threshold
,
Anti-Citrullinated Protein Antibodies - blood
2024
Background
Seropositive rheumatoid arthritis (RA) is associated with significant cardiovascular and pulmonary morbidity. However, screening for early detection of pulmonary involvement especially interstitial lung disease (ILD) is not established in RA.
Methods
We propose a non-invasive radiation-free approach to screen for interstitial lung involvement (ILI) by means of pulmonary function tests (PFT) and pleuro-pulmonary transthoracic ultrasound (LUS) with additional cardiopulmonary exercise tests (CPET) with ECG, and echocardiography. We included patients with confirmed diagnosis of seropositive RA according to ACR criteria, but without symptoms for or known cardiopulmonary disease. ILD was suspected when significant LUS abnormalities and additional PFT changes were present.
Results
We included 67 consecutive patients (78% female, mean age 61 ± 12 years, 48% active or previous smokers), who fulfilled the inclusion criteria and gave written informed consent.
We found 48% of patients with suspected changes in PFT with a diffusion capacity (DLCOc-SB) ≤ 80%, among them 7% with forced vital capacity (FVC) ≤ 80%.
In 40% of patients, we found noticeable changes in LUS, 24% with an ILD compatible pattern. In 16% of cases, LUS abnormalities and additional PFT changes were present, and ILI was suspected. Additional findings included obstructive lung disease (
n
= 11), subpleural consolidation (
n
= 6) including one confirmed lung cancer, minimal pleural effusion (
n
= 6), and ischemic cardiac disease (
n
= 2). None of the patients showed signs of pulmonary vascular involvement.
Conclusions
ILI was suspected in 16% of cases using a new radiation-free screening protocol in asymptomatic RA patients.
Trial registration
German Register of Clinical Studies (DRKS00028871).
Journal Article
Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?
2020
Background
Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma.
Case presentation
Here, we report the case of a 49-year-old woman with severe asthma and ABPA, who was uncontrolled despite maximum inhalative therapy, anti-IL5-Rα antibody and continuous oral steroid therapy. Moreover, trials of itraconazole as well as omalizumab showed insufficient efficacy. Lung function revealed peripheral obstruction. FeNO and IgE were increased, eosinophils were suppressed under treatment while marked increases had been documented previously. Switching to dupilumab led to a complete resolution of pulmonary symptoms, resolution of exacerbations and complete withdrawal of oral steroids. A drastic improvement in lung function was noted, with an increase in FEV1 of almost 1 l. FeNO was normalized and IgE strongly reduced.
Conclusion
Our case highlights that a patient may exhibit differential treatment responses to the currently available asthma biologics and suggests switching treatment if outcome is insufficient. A potential role for dupilumab in the treatment of ABPA warrants future studies.
Journal Article