Franziska C. Trudzinski

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.

Clinical implications of Mycobacterium chimaera detection in thermoregulatory devices used for extracorporeal membrane oxygenation (ECMO), Germany, 2015 to 2016

Mycobacterium chimaera, a non-tuberculous mycobacterium, was recently identified as causative agent of deep-seated infections in patients who had previously undergone open-chest cardiac surgery. Outbreak investigations suggested an aerosol-borne pathogen transmission originating from water contained in heater-cooler units (HCUs) used during cardiac surgery. Similar thermoregulatory devices are used for extracorporeal membrane oxygenation (ECMO) and M. chimaera might also be detectable in ECMO treatment settings. We performed a prospective microbiological study investigating the occurrence of M. chimaera in water from ECMO systems and in environmental samples, and a retrospective clinical review of possible ECMO-related mycobacterial infections among patients in a pneumological intensive care unit. We detected M. chimaera in 9 of 18 water samples from 10 different thermoregulatory ECMO devices; no mycobacteria were found in the nine room air samples and other environmental samples. Among 118 ECMO patients, 76 had bronchial specimens analysed for mycobacteria and M. chimaera was found in three individuals without signs of mycobacterial infection at the time of sampling. We conclude that M. chimaera can be detected in water samples from ECMO-associated thermoregulatory devices and might potentially pose patients at risk of infection. Further research is warranted to elucidate the clinical significance of M. chimaera in ECMO treatment settings.

Endoscopic Lung Volume Reduction Using Endobronchial Valves in Patients with Severe Emphysema and Very Low FEV1

Background: Patients with a forced expiratory volume in 1 s (FEV1) below 20% of the predicted normal values (pred.) and either homogeneous emphysema or low diffusing capacity for carbon monoxide (DLCO) have a high risk for adverse events including death when undergoing surgical lung volume reduction. Objectives: We hypothesized that selected patients can benefit from endoscopic lung volume reduction (eLVR) despite a very low FEV1. Methods: This study is a retrospective analysis of consecutive patients with severe airflow obstruction, an FEV1 ≤20% of pred., and low DLCO who were treated by eLVR with endobronchial valves (EBV) between June 2012 and January 2015. Pre- and postinterventional lung function parameters, the 6-min walking test (6-MWT) distance, adverse events, and follow-up were recorded. Results: In 20 patients, there was an overall improvement in lung function with an increase in FEV1 (16.97-21.03% of pred.) and a decrease in residual volume (322-270% of pred.) and total lung capacity (144-129.06% of pred.). The 6-MWT distance improved (from 239 ± 77 to 267± 97 m overall, and from 184 ± 50 to 237 ± 101 m if patients developed an atelectasis of the target lobe). Pneumothorax occurred in 5 of the 20 patients (25%). 30-day mortality was 0%, and all patients survived to discharge. Conclusions: The patients benefitted moderately from EBV treatment despite an initially low FEV1. Some patients improved remarkably. EBV treatment in patients with an FEV1 ≤20% of pred. is generally feasible and safe. The greatest risk is pneumothorax with prolonged chest tube duration.

The Homburg lung - efficacy and safety of a minimal-invasive pump-driven device for veno-venous extracorporeal carbon dioxide removal.

Extracorporeal carbon dioxide removal (ECCO2R) is increasingly considered a viable therapeutic approach in the management of hypercapnic lung failure to avoid intubation or to allow lung-protective ventilator settings. This study aimed to analyze efficacy and safety of a minimal-invasive ECCO2R device, the Homburg lung. The Homburg lung is a pump-driven system for veno-venous ECCO2R with ¼″ tubing and a 0.8 m2 surface oxygenator. Vascular access is usually established via a 19F/21 cm bilumen cannula in the right internal jugular vein. For this work, we screened patient registries from two German centers for patients who underwent ECCO2R with the Homburg lung because of hypercapnic lung failure since 2013. Patients who underwent extracorporeal membrane oxygenation before ECCO2R were excluded. Patients who underwent ECCO2R more than one time were only included once. In total, 24 patients (aged 53.86 ± 12.49 years; 62.5% male) were included in the retrospective data analysis. Ventilatory failure occurred because of chronic obstructive pulmonary disease (50%), cystic fibrosis (16.7%), acute respiratory distress syndrome (12.5%), and other origins (20.8%). The system generated a blood flow of 1.18 ± 0.23 liters per minute (lpm). Sweep gas flow was 3.87 ± 2.97 lpm. Within 4 hours, paCO2 could be reduced significantly from 82.05 ± 15.57 mm Hg to 59.68 ± 12.27 mm Hg, thereby, increasing pH from 7.23 ± 0.10 to 7.36 ± 0.09. Cannulation-associated complications were transient arrhythmia (1/24 patients) and air embolism (1/24). Fatal complications did not occur. In conclusion, the Homburg lung provides effective carbon dioxide removal in hypercapnic lung failure. The cannulation is a safe procedure, with complication rates comparable to those in central venous catheter implantation.

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.

Inhaled Sedation in Patients With Acute Respiratory Distress Syndrome Undergoing Extracorporeal Membrane Oxygenation.

Six patients suffering from acute respiratory distress syndrome with the need for extracorporeal membrane oxygenation (ECMO) therapy in deep sedation were included. Isoflurane sedation with the AnaConDa system was initiated within 24 hours after initiation of ECMO therapy and resulted in a satisfactory sedation (Richmond Agitation-Sedation Scale −4 to −5). Despite deep sedation, spontaneous breathing was possible in 6 of 6 patients. We observed a reduced need for vasopressor therapy and improved lung function (PaO2, PaCO2, delta P, and tidal volume) during isoflurane sedation. Opioid consumption could be reduced, and only very low doses of isoflurane were needed (1–3 mL/h). This small case series supports the feasibility of sedation using inhaled anesthetics concurrently with venovenous ECMO.

Lung Clearance Index is Increased in Patients with COPD - LCI Measurements in the Daily Routine

Objective: The lung clearance index (LCI), an index of ventilation homogeneity derived from the multiple breath wash out (MBW) of an inert gas, is a lung function test to monitor pulmonary disease. The aim of this study was to investigate whether LCI measurements are suitable for the daily routine in patients with COPD in comparison to young and healthy controls. Methods: MBW measurements were performed successfully in 23 patients (out of 42) patients with COPD (FEV1 %, 40.41 ± 14.65). As controls we selected 30 healthy and young volunteers. All subjects used the EasyOne ProLab™ (ndd, Switzerland). Results: 18 patients were not able to finish measurements successfully because of significant leaks, cough and irregular breathing (GOLD I n=1 (5.6%); GOLD II n=6 (33.3%); GOLD III n=5 (27.7%); GOLD IV n=6 (33.3%). The mean LCI was significantly higher in COPD patients as compared to young and healthy volunteers (12.55 ± 3.50 vs 7.00 ± 1.02, p<0.05). Although LCI correlated with FEV1 %of predicted (r²=-0.540, p<0.01) and Rtot (% pred.) (r²=0.504, p<0.01) the method failed to discriminate between GOLD II-IV classes. LCI correlated with the volume of trapped gas in elderly patients with COPD and young and healthy controls [FRC (% pred.) (r²=0.191, p<0.01), ITGV (% pred.) (r²=0.478, p<0.01), and RV (% pred.) (r²=0.462, p<0.01)]. Moreover, the results did not correlate with the 6-MWT, a validated clinical outcome parameter. Conclusions: Although measurement of LCI was capable to detect inhomogeneous ventilation (airway obstruction and hyperinflation), this method did not discriminate between GOLD II-IV and did not correlate with 6-MWT. More than 43% of the patients with COPD did not complete the study because of difficulties with the method. Nevertheless, the LCI might be a tool to gain insight into lung pathophysiology in younger patients e.g. children. Our preliminary study encourages further investigations for the future.

Extracorporeal membrane oxygenation (ECMO) as salvage treatment for pulmonary Echinococcus granulosus infection with acute cyst rupture

Extracorporeal membrane oxygenation (ECMO) has been used successfully for the treatment of patients with respiratory failure due to severe infections. Although rare, parasites can also cause severe pulmonary disease. Tapeworms of the genus Echinococcus give rise to the development of cystic structures in the liver, lungs, and other organs. Acute cyst rupture leads to potentially life-threatening infection, and affected patients may deteriorate rapidly. The case of a young woman from Bulgaria who was admitted to hospital with severe dyspnoea, progressive chest pain, and haemoptysis is described. Computed tomography of the chest was pathognomonic for cystic echinococcosis with acute cyst rupture. Following deterioration on mechanical ventilation, she was cannulated for veno-venous ECMO. The patients condition improved considerably, and she was weaned successfully from ECMO and mechanical ventilation. Following lobectomy of the affected left lower lobe, the patient was discharged home in good condition. This appears to be the first report of the successful use of ECMO as salvage treatment for a severe manifestation of a helminthic disease. Due to recent migration to Western Europe, the number of patients presenting with respiratory failure due to pulmonary echinococcosis with cyst rupture is likely to increase.

Microbiological airway colonization in COPD patients with severe emphysema undergoing endoscopic lung volume reduction

Background Endoscopic lung volume reduction (eLVR) is a therapeutic option for selected patients with COPD and severe emphysema. Infectious exacerbations are serious events in these vulnerable patients; hence, prophylactic antibiotics are often prescribed postinterventionally. However, data on the microbiological airway colonization at the time of eLVR are scarce, and there are no evidence-based recommendations regarding a rational antibiotic regimen. Objective The aim of this study was to perform a clinical and microbiological analysis of COPD patients with advanced emphysema undergoing eLVR with endobronchial valves at a single German University hospital, 2012–2017. Patients and methods Bronchial aspirates were obtained prior to eLVR and sent for microbiological analysis. Antimicrobial susceptibility testing of bacterial isolates was performed, and pathogen colonization was retrospectively compared with clinical parameters. Results At least one potential pathogen was found in 47% (30/64) of patients. Overall, Gram-negative bacteria constituted the most frequently detected pathogens. The single most prevalent species were Haemophilus influenzae (9%), Streptococcus pneumoniae (6%), and Staphylococcus aureus (6%). No multidrug resistance was observed, and Pseudomonas aeruginosa occurred in <5% of samples. Patients without microbiological airway colonization showed more severe airflow limitation, hyperinflation, and chronic hypercapnia compared to those with detected pathogens. Conclusion Microbiological airway colonization was frequent in patients undergoing eLVR but not directly associated with poorer functional status. Resistance testing results do not support the routine use of antipseudomonal antibiotics in these patients.

Expression of mRNA for IL-22 Binding Protein in the Broncheoalveolar Fluid after Inhaled Allergen Challenge in Subjects with Asthma

Background: T helper (Th)17/22 cells may play a role in allergic asthma. Recent findings showed increased mRNA expression for IL-22 in peripheral blood mononuclear cells (PBMC) from patients with asthma. Thereby, the role of the natural antagonist of IL-22, IL-22 binding protein (IL-22 BP), a soluble receptor for IL-22, remains to be elucidated. In this study, we investigate the expression of mRNA for IL-22 BP in individuals with asthma. Methods: We assessed the effect of allergen inhalation challenge on mRNA-expression for IL-22 and IL-22 BP, and IL-22 receptor in mononuclear cells of the broncheoalveolar fluid (BALF) from individuals with allergic asthmatic. Furthermore, in vitro we investigated mRNA expression for IL-22 and IL-22 BP, and IL 22 receptor after costimulation of peripheral blood mononuclear cells (PBMC) from individuals with asthma and normal controls with Th2 cytokines IL-4, IL-9, and GM-CSF in a time-dependent manner. Results: The expression of mRNA for IL-22-BP in PBMCs from healthy controls and individuals with asthma could be found after co-stimulation with IL-4 after a minimum of 12 hours, which hold on for 96 hours. The expression of mRNA for IL-22 BP in subjects with atopic asthma was discovered in mononuclear cells of the BALF after segmental allergen inhalation challenge. Our findings suggest a possible role for IL-22 BP in allergen-induced airway responses.