Sebastian Fähndrich

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.

Sex differences in alpha-1-antitrypsin deficiency lung disease-analysis from the German registry

Abstract Alpha-1-antitrypsin deficiency (AATD) is a rare condition with clinical mani-festations of the lung and the liver. There is evidence that the gender affects the clinical presentation of non-AATD chronic obstructive lung disease (COPD). The aim of this study was to analyze gender-dependent disease pattern in AATD-based COPD. Data from 1066 individuals from the German AATD registry were analyzed by descriptive and analytical statistics. The AAT genotypes comprised 820 individuals with PiZZ (male 56%, female 45%), 109 with PI SZ (male 55%; female 45%), and others (n = 137). A subgroup of 422 patients with available post-bronchodilator FEV1% predicted was analyzed in detail after stratification in spirometric GOLD stages I-IV. The age of the registered individuals is 52.2 ± 13.4 years (male: 51.91 ± 13.86 years; female: 52.76 ± 13.39 years). Female patients with GOLD I-IV showed lower numbers of pack-years and lower BMI. The time between the first symptom and the establishment of the correct diagnosis was significantly longer in female (14.47 ± 16.46 years) as compared to male individuals (12.39 ± — 14.38 years, p = 0.04). In conclusion, the data of the registry allow to characterize the natural course of the disease and highlight differences in the clinical presentation of patients with AATD-dependent COPD.

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.

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.

Relationship of hyperlipidemia to comorbidities and lung function in COPD: Results of the COSYCONET cohort

Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1–4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV1) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication.

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.

Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency – analysis from the German Registry

Background Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary disease that is associated with a higher risk to develop chronic obstructive pulmonary disease and liver cirrhosis. Previous cross-sectional studies on AATD individuals have shown a relationship between worse St George’s Respiratory Questionnaire (SGRQ) scores and elevated exacerbation rate or high cigarette consumption. There is a lack of longitudinal data on the relationship between the exacerbation rate and worsening of SGRQ during disease. The aim of this study was to provide not only cross-sectional data but also information about the deterioration in quality of life over a follow-up period up to 7 years (median follow-up period of 3.33 years). Methods We investigated questionnaire-based data of the German AATD registry concerning the relationship between SGRQ and exacerbation frequency, smoking history, forced expiratory volume in 1 second (FEV1) and carbon monoxide diffusion capacity (DLCO) first in cross-sectional analysis and later in longitudinal analysis. Results Eight hundred sixty-eight individuals with protease inhibitor ZZ (PiZZ) genotype with an average age of 52.6±12.8 years had an SGRQ score of 45.7±20.6. SGRQ significantly correlated with the exacerbation frequency within the last 2 years (r=0.464; P<0.001), smoking history (r=0.233; P<0.001), FEV1 (r=−0.436; P<0.001), DLCO (r=−0.333; P<0.001), and patients’ age (r=0.292; P<0.001). Individuals with occupational dust exposure had significantly worse quality of life (P<0.001). Mean annual deterioration of SGRQ in all patients with available follow-up data (n=286) was 1.21±4.45 points per year. Univariate and multivariate analysis showed a significant relationship between worsening of SGRQ/year and exacerbation frequency in the follow-up period (r=0.144; P=0.015). Conclusion Worsening of SGRQ is associated with the exacerbation frequency in individuals with PiZZ AATD.

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.

Alpha-1-Antitrypsin-Mangel: Pathophysiologie, Diagnostik und Therapie

ZusammenfassungDie chronisch obstruktive Lungenerkrankung (COPD) ist eine durch inhalative Noxen hervorgerufene chronische Erkrankung, deren Phänotyp neben Umwelteinflüssen auch durch genetische Ursachen wie einem Alpha-1-Antitrypsin(AAT)-Mangel beeinflusst wird, eine Genotypisierung kann mittels Polymerasekettenreaktion und Sequenzierung erfolgen. Um eine Progression der Erkrankung zu verlangsamen, kann AAT substituiert werden.

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.