Role of multidrug-resistant bacteria in weaning from invasive mechanical ventilation.

BACKGROUND: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. METHODS: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). RESULTS: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). CONCLUSION: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD. RESEARCH QUESTION: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD. METHODS: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses. RESULTS: Among 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density. INTERPRETATION: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care. METHODS: We focused on cardiovascular comorbidities, blood high sensitivity troponin (hs-troponin) and lipid profiles in COPD patients with and without AATD. We used clinical data from six German University Medical Centres of the MIRACUM (Medical Informatics Initiative in Research and Medicine) consortium. The codes for the international classification of diseases (ICD) were used for COPD as a main diagnosis and for comorbidities and blood laboratory data were obtained. Data analyses were based on the DataSHIELD framework. RESULTS: Out of 112,852 visits complete information was available for 43,057 COPD patients. According to our findings, 746 patients with AATD (1.73%) showed significantly lower total blood cholesterol levels and less cardiovascular comorbidities than non-AATD COPD patients. Moreover, after adjusting for the confounder factors, such as age, gender, and nicotine abuse, we confirmed that hs-troponin is a suitable predictor of overall mortality in COPD patients. The comorbidities associated with AATD in the current study differ from other studies, which may reflect geographic and population-based differences as well as the heterogeneous characteristics of AATD. CONCLUSION: The concept of MIRACUM is suitable for the analysis of a large healthcare database. This study provided evidence that COPD patients with AATD have a lower cardiovascular risk and revealed that hs-troponin is a predictor for hospital mortality in individuals with COPD.

High-sensitivity troponin I and all-cause mortality in patients with stable COPD: an analysis of the COSYCONET study.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death with a considerable part of the population dying from cardiovascular diseases. High-sensitivity troponin I (hs-TnI) might help to better identify COPD patients at high risk of mortality. We aimed to study the predictive value of hs-TnI for all-cause mortality beyond established COPD assessments, and after consideration of relevant cardiovascular risk factors and prevalent cardiovascular diseases, in a broad population with stable COPD.Circulating hs-TnI concentrations together with a wide range of respiratory and cardiovascular markers were evaluated in 2085 patients with stable COPD across all severity stages enrolled in the multicentre COSYCONET cohort study. The primary outcome was all-cause mortality over 3 years of follow-up.Hs-TnI was detectable in 2020 (96.9%) patients. The median hs-TnI concentration was 3.8 ng·L-1 (interquartile range 2.5-6.6 ng·L-1), with levels above the 99th percentile reference limit of 27 ng·L-1 observed in 1.8% of patients. In Cox regression analyses including adjustments for airflow limitation, dyspnoea grade, exercise capacity and history of severe exacerbations, as well as traditional cardiovascular risk factors, estimated glomerular filtration rate, ankle-brachial index, N-terminal pro-brain natriuretic peptides and prevalent cardiovascular diseases, hs-TnI was a significant predictor for all-cause mortality, both as a continuous variable (hazard ratio (HR) for log hs-TnI 1.28, 95% CI 1.01-1.62) and categorised according to the cut-off of 6 ng·L-1 (HR 1.63, 95% CI 1.10-2.42).In patients with stable COPD, hs-TnI is a strong predictor of all-cause mortality beyond established COPD mortality predictors, and independent of a broad range of cardiovascular risk factors and prevalent cardiovascular diseases. Hs-TnI concentrations well below the upper reference limit provide further prognostic value for all patients with COPD when added to established risk assessments.

COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment.

BACKGROUND: Most cases of COVID-19 are considered mild, but patients with immunosuppressant treatment might be prone to severe courses of disease. Expert panels advise to delay treatment with cell-depleting MS therapies during the COVID-19 pandemic. METHODS: We report a case of a patient with relapsing-remitting multiple sclerosis who developed COVID-19 pneumonia 2 weeks after the first week of cladribine therapy. RESULTS: Despite a severe lymphopenia (absolute lymphocyte count 240/µL), the patient had a moderate course of COVID-19. CONCLUSION: Apart from maximal supportive treatment, this could be due to cladribine reducing inflammatory response, which probably contributes considerably to severe courses of COVID-19 pneumonia.

Consequences of chronic kidney disease in chronic obstructive pulmonary disease.

BACKGROUND: The combination of chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) is associated with a higher prevalence of comorbidities and increased mortality. The impact of kidney function on patient-centered outcomes in COPD has not been evaluated. METHODS: Patients from the German COPD and Systemic Consequences - Comorbidities Network (COSYCONET) cohort COPD were analysed. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) measurements were < 60 mL/min/1.73m2 at study inclusion and six month later. The effect of CKD, on comorbidities, symptoms [modified British Medical Research Council dyspnoea scale], physical capacity [six-minute walk test, and timed up and go] and St George's Respiratory Questionnaire were analysed. Restricted cubic spline models were used to evaluate a nonlinear relationship between eGFR with patient-centered outcomes, cox survival analysis was applied to evaluate mortality. RESULTS: 2274 patients were analysed, with CKD diagnosed in 161 (7.1%). Spline models adjusted for age, gender, BMI, FEV1 and cardiovascular comorbidities revealed independent associations between eGFR with modified British Medical Research Council dyspnoea scale, St George's Respiratory Questionnaire, (p < 0.001 and p = 0.011), six-minute walk test (p = 0.015) and timed up and go (p < 0.001). CKD was associated with increased mortality, independently from for other cardiovascular comorbidities (hazard ratio 2.3; p < 0.001). CONCLUSION: These data show that CKD is a relevant comorbidity in COPD patients which impacts on patient-centered outcomes and mortality. TRIAL REGISTRATION: NCT01245933.

Cardiovascular risk in patients with alpha-1-antitrypsin deficiency.

BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a rare inherited condition caused by mutations of the SERPINA1 gene that is associated with the development of a COPD like lung disease. The comorbidities in patients with AATD-related lung diseases are not well defined. The aim of this study was to analyze the clinical phenotype of AATD patients within the German COPD cohort study COSYCONET ("COPD and SYstemic consequences-COmorbidities NETwork") cohort focusing on the distribution of comorbidities. METHOD AND RESULTS: The data from 2645 COSYCONET patients, including 139 AATD patients (110 with and 29 without augmentation therapy), were analyzed by descriptive statistics and regression analyses. We found significantly lower prevalence of cardiovascular comorbidities in AATD patients as compared to non-AATD COPD patients. After correction for age, pack years, body mass index, and sex, the differences were still significant for coronary artery disease (p = 0.002) and the prevalence of peripheral artery disease as determined by an ankle-brachial-index <= 0.9 (p = 0.035). Also the distribution of other comorbidities such as bronchiectasis differed between AATD and non-deficient COPD. CONCLUSION: AATD is associated with a lower prevalence of cardiovascular disease, the underlying mechanisms need further investigation.

Outcome of Patients with Interstitial Lung Disease Treated with Extracorporeal Membrane Oxygenation for Acute Respiratory Failure.

RATIONALE: Patients with interstitial lung disease and acute respiratory failure have a poor prognosis especially if mechanical ventilation is required. OBJECTIVES: To investigate the outcome of patients with acute respiratory failure in interstitial lung disease undergoing extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or transplantation. METHODS: This was a retrospective analysis of all patients with interstitial lung disease and acute respiratory failure treated with or without ECMO from March 2012 to August 2015. MEASUREMENTS AND MAIN RESULTS: Forty patients with interstitial lung disease referred to our intensive care unit for acute respiratory failure were included in the analysis. Twenty-one were treated with ECMO. Eight patients were transferred by air from other hospitals within a range of 320 km (linear distance) for extended intensive care including the option of lung transplant. In total, 13 patients were evaluated, and eight were finally found to be suitable for lung transplantation from an ECMO bridge. Four patients from external hospitals were de novo listed during acute respiratory failure. Six patients underwent lung transplant, and two died on the waiting list after 9 and 63 days on ECMO, respectively. A total of 14 of 15 patients who did not undergo lung transplantation (93.3%) died after 40.3 ± 27.8 days on ECMO. Five out of six patients (83.3%) receiving a lung transplant could be discharged from hospital. CONCLUSIONS: ECMO is a lifesaving option for patients with interstitial lung disease and acute respiratory failure provided they are candidates for lung transplantation. ECMO is not able to reverse the poor prognosis in patients that do not qualify for lung transplantation.

Increase of Mast Cell-Nerve Association and Neuropeptide Receptor Expression on Mast Cells in Perennial Allergic Rhinitis.

OBJECTIVES: Mast cells (MCs) and nerves play an important role in allergic rhinitis (AR), but little is known about their crosstalk in AR. The aim of this study was to investigate MC-nerve interaction in the human nasal mucosa during AR. METHODS: The association between MCs and nerves, the expression of neuropeptide receptors (neurokinin 1 receptor [NK1R], neurokinin 2 receptor [NK2R], calcitonin gene-related peptide receptor [CGRPR], and MrgX2) on MCs, and protease-activated receptor 2 (PAR2) and tyrosine receptor kinase A (TrkA) on nerve fibres in the human nasal mucosa were investigated with immunofluorescence and real-time PCR. RESULTS: The association between MCs and nerves was found to be significantly increased, although the numbers of MCs and nerve fibres were unchanged during AR. MCs expressing tryptase-chymase (MCtc) were frequently associated with nerve fibres and these contacts increased significantly in AR. Neuropeptide receptors NK1R, NK2R, and CGRPR were firstly found to be largely localised on MCs. The number of MCs expressing NK1R and NK2R, but not CGRPR, was significantly increased in AR. Interestingly, MCtc mostly expressed these neuropeptide receptors. The newly discovered tachykinin receptor MrgX2 was not expressed on nasal MCs, but was expressed on gland cells and increased in AR. Additionally, tachykinergic nerve fibres were found to express PAR2 or TrkA as receptors for MCs. CONCLUSIONS: This study revealed for the first time an increase of MC-nerve association and neuropeptide receptor expression on MCs during AR as well as nerve fibres containing receptors for MCs. These results suggest that targeting or controlling airway sensory nerve function as a modulator of MCs may prevent allergic airway inflammation such as AR.

Bilateral Endoscopic Lung Volume Reduction in Patients with Severe Emphysema.

Reducing hyperinflated areas in chronic obstructive pulmonary disease, either surgically or endoscopically, leads to improvement of functional parameters. It is unclear if bilateral treatment with endobronchial valves (EBV) aiming at total lobar occlusion is beneficial. The aim of this study was to assess the results after staged bilateral endoscopic treatment with EBV. This is a retrospective analysis of patients with severe airflow obstruction, who were treated bilaterally with EBV in two stages, aiming at subsequent atelectasis. Pre- and postintervention lung function parameters, the 6-minute walk test (6-MWT), complications, and follow-up were recorded. Sixteen patients were treated bilaterally in two stages. There was an overall improvement in lung function from baseline to second-treatment follow-up with an increase in FEV1 (23.57-29.21% of predicted) and a decrease in residual volume (299.21-240.10% of predicted) and total lung capacity (140.78-128.71% of predicted). The 6-MWT improved up to 54 m. After each procedure, 9 of 16 patients (56.25%) developed an atelectasis of the target lobe. Overall, pneumothorax occurred in 8 of 32 procedures (25%). No patient died. Patients benefitted from the first EBV treatment. The second treatment did not lead to marked improvements compared to the first treatment. Bilateral lung volume reduction with valves is possible; however, the current results seem not to justify bilateral valve treatment as a routine approach.