External Validation of the PREdiction of Survival on Extracorporeal Membrane Oxygenation Therapy (PRESET) Score: A Single Center Cohort Experience.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition affecting >10% of intensive care unit (ICU) patients worldwide with a mortality of up to 59% depending on severity. Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving procedure in severe ARDS but is technically and financially challenging. In recent years, various scoring systems have been proposed to select patients most likely to benefit from ECMO, with the PREdiction of Survival on ECMO Therapy (PRESET) score being one of the most used. We collected data from 283 patients with ARDS of various etiology who underwent veno-venous (V-V) ECMO therapy at a German tertiary care ICU from January 2012 to December 2022. Median age in the cohort was 56 years, and 64.31% were males. The in-hospital mortality rate was 50.88% (n = 144). The median (25%; 75% quartile) severity scores were 38 (31; 49) for Simplified Acute Physiology Score (SAPS) II, 12 (10; 13) for Sequential Organ Failure Assessment (SOFA) and 7 (5; 8) for PRESET. Simplified Acute Physiology Score-II displayed the best prognostic value (area under the receiver operating characteristic [AUROC]: 0.665 [confidence interval (CI): 0.574-0.756; p = 0.046]). Prediction performance was weak in all analyzed scores despite good calibration. Simplified Acute Physiology Score-II had the best discrimination after adjustment of our original cohort. The use of scores explored in this study for patient selection for eligibility for V-V ECMO is not recommendable.

Comparison of post-COVID-19 symptoms in patients infected with the SARS-CoV-2 variants delta and omicron-results of the Cross-Sectoral Platform of the German National Pandemic Cohort Network (NAPKON-SUEP).

PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

[Alpha 1-antitrypsin deficiency]. / Alpha-1-Antitrypsin-Mangel.

Alpha 1­antitrypsin (AAT) deficiency represents a complex genetic disorder and necessitates an interdisciplinary approach in the clinical practice. This article provides an overview of the epidemiology, genetics, symptoms, diagnostics and treatment of AAT deficiency. Knowledge and an in-depth understanding of AAT deficiency are indispensable to improve the early recognition of AAT, to optimize the quality of life of those affected and to enable targeted treatment interventions.

Two single lung transplantations from one donor: lung twinning in the LAS era.

OBJECTIVES: The implementation of the Lung Allocation Score (LAS) in the Eurotransplant international collaborative framework decreased waiting list mortality, but organ shortage remains a significant problem. Transplantation of two single lungs from one donor into two recipients (lung twinning) may decrease waiting list mortality. We sought to analyze if this strategy can lead to an acceptable intermediate-term outcome. METHODS: Since the LAS-implementation we performed 32 paired single-lung transplantations from 16 postmortal donors. Data and outcome were analyzed retrospectively comparing recipients receiving the first lung (first twins) with recipients receiving the second lung (second twins), left versus right transplantation and restrictive versus obstructive disease. RESULTS: Survival at one year was 81% and 54% at five years. Veno-venous ECMO had been successfully used as bridge-to-transplant in three patients with ECMO-explantation immediately after surgery. Bronchial anastomotic complications were not observed in any patient. First twins and second twins exhibited similar survival (p = 0.82) despite higher LAS in first twins (median 45 versus 34, p < 0.001) and longer cold ischemic time in second twins (280 ± 83 vs. 478 ± 125 min, p < 0.001). Survival of left and right transplantation was similar (p = 0.45) with similar best post-transplant FEV1 (68 ± 15% versus 62 ± 14%, p = 0.26). Survival was similar in restrictive and obstructive disease (p = 0.28) with better post-transplant FEV1 (70 ± 15% versus 57 ± 11%, p = 0.02) in restrictive disease. CONCLUSIONS: Performing two single-lung transplantations from one donor can be performed safely with encouraging intermediate-term outcome and good functional capacity. Lung twinning maximizes the donor pool and may help to overcome severe organ shortage. CLINICAL TRIALS: This research is not a clinical trial. Thus no registration details will be provided.

Effects of triple therapy on disease burden in patients of GOLD groups C and D: results from the observational COPD cohort COSYCONET.

BACKGROUND: Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting. METHODS: Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes. RESULTS: In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed. CONCLUSION: Without statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds.

Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence.

Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicin-induced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing.

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.

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

BACKGROUND & AIMS: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown. METHODS: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi∗ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi∗ZZ adults with and 35 without augmentation. RESULTS: Compared with nonaugmented subjects, augmented Pi∗ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted. CONCLUSIONS: The first evaluation of AAT augmentation on the Pi∗ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi∗ZZ-associated liver disease.

Mutual Regulation of Transcriptomes between Murine Pneumocytes and Fibroblasts Mediates Alveolar Regeneration in Air-Liquid Interface Cultures.

Alveolar type 2 and club cells are part of the stem cell niche of the lung and their differentiation is required for pulmonary homeostasis and tissue regeneration. A disturbed crosstalk between fibroblasts and epithelial cells contributes to the loss of lung structure in chronic lung diseases. Therefore, it is important to understand how fibroblasts and lung epithelial cells interact during regeneration. Here, we analyzed the interaction of fibroblasts and the alveolar epithelium modeled in air-liquid interface cultures. Single-cell transcriptomics showed that cocultivation with fibroblasts leads to increased expression of type 2 markers in pneumocytes, activation of regulons associated with the maintenance of alveolar type 2 cells (e.g., Etv5), and transdifferentiation of club cells toward pneumocytes. This was accompanied by an intensified transepithelial barrier. Vice versa, the activation of NF-κB pathways and the CEBPB regulon and the expression of IL-6 and other differentiation factors (e.g., fibroblast growth factors) were increased in fibroblasts cocultured with epithelial cells. Recombinant IL-6 enhanced epithelial barrier formation. Therefore, in our coculture model, regulatory loops were identified by which lung epithelial cells mediate regeneration and differentiation of the alveolar epithelium in a cooperative manner with the mesenchymal compartment.

Characteristics of Current Smokers versus Former Smokers with COPD and Their Associations with Smoking Cessation Within 4.5 Years: Results from COSYCONET.

Background: Many patients with chronic obstructive pulmonary disease (COPD) continue smoking. We used data from the "real-life" COSYCONET COPD cohort to evaluate whether these patients differed from patients with COPD who either had ceased smoking prior to inclusion or ceased during the follow-up time of the study. Methods: The analysis was based on data from visits 1-5 (covering 4.5 years), including all patients with the diagnosis of COPD who were either ex-smokers or smokers and categorized as GOLD 1-4 or the former GOLD 0 category. We compared the characteristics of smokers and ex-smokers at baseline (visit 1), as well as the course of lung function in the follow-up of permanent ex-smokers, permanent smokers and incident ex-smokers (smokers at visit 1 who ceased smoking before visit 5). We also identified baseline factors associated with subsequent smoking cessation. Results: Among 2500 patients who were ever-smokers, 660 were current smokers and 1840 ex-smokers at baseline. Smokers were younger than ex-smokers (mean 61.5 vs 66.0 y), had a longer duration of smoking but fewer pack-years, a lower frequency of asthma, higher forced expiratory volume in 1 sec (FEV1, 59.4 vs 55.2% predicted) and higher functional residual capacity (FRC, 147.7 vs 144.3% predicted). Similar results were obtained for the longitudinal subpopulation, comprising 713 permanent ex-smokers, 175 permanent smokers, and 55 incident ex-smokers. When analyzing the time course of lung function, higher FRC, lower FEV1 and the presence of asthma (p < 0.05 each) were associated with incident cessation prior to visit 5, while less airway obstruction was associated with smoking continuation. Conclusion: These findings, which were consistent in the cross-sectional and longitudinal analyses, suggest that lung hyperinflation was associated with being or becoming ex-smoker. Possibly, it is perceived by patients as one of the factors motivating their attempts to quit smoking, independent from airway obstruction.

Clinical factors linked to the type of respiratory medication in COPD: results from the COSYCONET cohort.

BACKGROUND: The use of maintenance medication in patients with chronic obstructive pulmonary disease (COPD) in real life is known to deviate from recommendations in guidelines, which are largely based on randomized controlled trials and selected populations. OBJECTIVES: We used the COSYCONET (COPD and Systemic Consequences - Comorbidities Network) cohort to analyze factors linked to the use of COPD drugs under non-interventional circumstances. DESIGN: COSYCONET is an ongoing, multi-center, non-interventional cohort of patients with COPD. METHODS: Patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 0-4 participating in visits 1-5 were included. Data covered the period from 2010 to 2018. Generalized linear models were used to examine the relation of COPD characteristics to different types of respiratory medication. RESULTS: A total of 1043 patients were included. The duration of observation was 4.5 years. Use of respiratory medication depended on GOLD grades 0-4 and groups A-D. Long-acting muscarinic antagonist therapy increased over time, and was associated with low carbon monoxide (CO) diffusing capacity, while inhaled corticosteroid (ICS) use decreased. Active smoking was associated with less maintenance therapy in general, and female sex with less ICS use. From the eight items of the COPD Assessment Test, only hill and stair climbing were consistently linked to treatment. CONCLUSION: Using data from a large, close to real-life observational cohort, we identified factors linked to the use of various types of respiratory COPD medication. Overall, use was consistent with GOLD recommendations. Beyond this, we identified other correlates of medication use that may help us to understand and improve therapy decisions in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933.

Impact of the COVID-19 pandemic on well-being and quality of life of patients with alpha-1-antitrypsin deficiency.

BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder characterized by mutations in the SERPINA1 gene, primarily affecting the lungs and liver. The COVID-19 pandemic has raised questions about the susceptibility of individuals with AATD to COVID-19 and whether patients with rare lung disease might experience increased stress-related symptoms and mental health challenges. This study aims to investigate the impact of the COVID-19 pandemic on the quality of life of individuals living with AATD. METHODS: The study enrolled participants from the German registry for individuals with AATD. Questionnaires were sent to the 1250 participants, and a total of 358 patients were included in the analysis. The primary objective was to examine the influence of sociodemographic and disease-related factors on the occurrence of stress-related symptoms. This was accomplished through correlation and regression analyses. We also investigated the role of baseline quality of life (QoL), as measured by the St. George's Respiratory Questionnaire (SGRQ), as a mediator of this relationship. RESULTS: Stress-related symptoms were predicted by young age, female gender, psychological disorders, and a history of exacerbations of lung disease, as determined by multiple regression analysis. QoL as measured by the SGRQ mediated the relationship between poor lung function, stress, and a decline in overall well-being. CONCLUSION: The presented data demonstrate that the COVID-19 pandemic significantly affects the psychological well-being of patients with rare diseases, leading to increased levels of anxiety and stress. Disease-related factors can exacerbate stress manifestations, especially when compounded by sociodemographic and contextual factors. Thus, our study emphasizes the crucial role of taking these factors into account when managing individuals with AATD in pandemic situations.

Comparison of Serial and Parallel Connections of Membrane Lungs against Refractory Hypoxemia in a Mock Circuit.

Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy method for the treatment of severe hypoxic lung injury. In some cases, oxygen saturation and oxygen partial pressure in the arterial blood are low despite ECMO therapy. There are case reports in which patients with such instances of refractory hypoxemia received a second membrane lung, either in series or in parallel, to overcome the hypoxemia. It remains unclear whether the parallel or serial connection is more effective. Therefore, we used an improved version of our full-flow ECMO mock circuit to test this. The measurements were performed under conditions in which the membrane lungs were unable to completely oxygenate the blood. As a result, only the photometric pre- and post-oxygenator saturations, blood flow and hemoglobin concentration were required for the calculation of oxygen transfer rates. The results showed that for a pre-oxygenator saturation of 45% and a total blood flow of 10 L/min, the serial connection of two identical 5 L rated oxygenators is 17% more effective in terms of oxygen transfer than the parallel connection. Although the idea of using a second membrane lung if refractory hypoxia occurs is intriguing from a physiological point of view, due to the invasiveness of the solution, further investigations are needed before this should be used in a wider clinical setting.

Erratum: Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/ß-catenin signaling: Erratum.

[This corrects the article DOI: 10.7150/thno.30726.].

Transfer of Veno-venous Extracorporeal Membrane Oxygenation Patients With COVID-19 Associated Acute Respiratory Distress Syndrome.

Interhospital transport of acute respiratory distress syndrome (ARDS) patients bears transport-associated risks. It is unknown how interhospital extracorporeal membrane oxygenation (ECMO) transfer of COVID-19 patients by mobile ECMO units affects ARDS mortality. We compared the outcome of 94 COVID-19 patients cannulated in primary care hospitals and retrieved by mobile ECMO-teams to that of 84 patients cannulated at five German ECMO centers. Patients were recruited from March 2020 to November 2021. Twenty-six transports were airborne, 68 were land-based. Age, sex, body-mass-index, Simplified Acute Physiology Score (SAPS) II, days invasively ventilated, and P/F-Ratio before ECMO initiation were similar in both groups. Counting only regional transports (≤250 km), mean transport distance was 139.5 km ± 17.7 km for helicopter (duration 52.5 ± 10.6 minutes) and 69.8 km ± 44.1 km for ambulance or mobile intensive care unit (duration 57.6 ± 29.4 minutes). Overall time of vvECMO support (20.4 ± 15.2 ECMO days for transported patients vs. 21.0 ± 20.5 for control, p = 0.83) and days invasively ventilated (27.9 ± 18.1 days vs. 32.6 ± 25.1 days, p = 0.16) were similar. Overall mortality did not differ between transported patients and controls (57/94 [61%] vs. 51/83 [61%], p = 0.43). COVID-19 patients cannulated and retrieved by mobile ECMO-teams have no excess risk compared with patients receiving vvECMO at experienced ECMO centers. Patients with COVID-19-associated ARDS, limited comorbidities, and no contraindication for ECMO should be referred early to local ECMO centers.

[Smoking cessation in hospitalised patients - Initiate among inpatients, continue when outpatients - A Position Paper by the German Respiratory Society (DGP) Taskforce for Smoking Cessation]. / Tabakentwöhnung bei hospitalisierten Patienten:innen ­ Stationär einleiten, ambulant fortführen.

Tobacco smoking is the greatest preventable health risk. The effects are serious, both individually and societal. Nevertheless, the current prevalence of tobacco smokers in Germany is still high at around 35 %. A recent strong increase in actively smoking adolescents (14- to 17-year-olds, current prevalence approx. 16 %) and young adults (18- to 24-year-olds, current prevalence approx. 41 %) is also a cause for concern. About a third of all inpatients continue smoking while being treated. The hospitalization of active smokers in acute and rehabilitation hospitals serves as a "teachable moment" for initiation of cessation offers. An intervention that begins in hospital and continues for at least a month after discharge results in about 40 % additional smokefree patients. It is scientifically well-researched, effective and cost-efficient. After initiation in hospital these measures can be continued via ambulatory cessation programs, rehabilitation facilities, an Internet or telephone service. In Germany, there are structured and quality-assured cessation offers, both for the inpatient and for the outpatient area. The biggest obstacle to broad establishment of such offers is the lack of reimbursement. Two feasible ways to change this would be the remuneration of the existing OPS 9-501 "Multimodal inpatient treatment for smoking cessation" and the establishment of quality contracts according to §â€Š110a SGB V. An expansion of tobacco cessation measures in healthcare facilities would reduce smoking prevalence, associated burden of disease and consecutive costs.

MetaProFi: an ultrafast chunked Bloom filter for storing and querying protein and nucleotide sequence data for accurate identification of functionally relevant genetic variants.

MOTIVATION: Bloom filters are a popular data structure that allows rapid searches in large sequence datasets. So far, all tools work with nucleotide sequences; however, protein sequences are conserved over longer evolutionary distances, and only mutations on the protein level may have any functional significance. RESULTS: We present MetaProFi, a Bloom filter-based tool that, for the first time, offers the functionality to build indexes of amino acid sequences and query them with both amino acid and nucleotide sequences, thus bringing sequence comparison to the biologically relevant protein level. MetaProFi implements additional efficient engineering solutions, such as a shared memory system, chunked data storage and efficient compression. In addition to its conceptual novelty, MetaProFi demonstrates state-of-the-art performance and excellent memory consumption-to-speed ratio when applied to various large datasets. AVAILABILITY AND IMPLEMENTATION: Source code in Python is available at https://github.com/kalininalab/metaprofi.

Standardized airway wall thickness Pi10 from routine CT scans of COPD patients as imaging biomarker for disease severity, lung function decline, and mortality.

BACKGROUND: Chest computed tomography (CT) is increasingly used for phenotyping and monitoring of patients with COPD. The aim of this work was to evaluate the association of Pi10 as a measure of standardized airway wall thickness on CT with exacerbations, mortality, and response to triple therapy. METHODS: Patients of GOLD grades 1-4 of the COSYCONET cohort with prospective CT scans were included. Pi10 was automatically computed and analyzed for its relationship to COPD severity, comorbidities, lung function, respiratory therapy, and mortality over a 6-year period, using univariate and multivariate comparisons. RESULTS: We included n = 433 patients (61%male). Pi10 was dependent on both GOLD grades 1-4 (p = 0.009) and GOLD groups A-D (p = 0.008); it was particularly elevated in group D, and ROC analysis yielded a cut-off of 0.26 cm. Higher Pi10 was associated to lower FEV1 % predicted and higher RV/TLC, moreover the annual changes of lung function parameters (p < 0.05), as well as to an airway-dominated phenotype and a history of myocardial infarction (p = 0.001). These associations were confirmed in multivariate analyses. Pi10 was lower in patients receiving triple therapy, in particular in patients of GOLD groups C and D. Pi10 was also a significant predictor for mortality (p = 0.006), even after including multiple other predictors. CONCLUSION: In summary, Pi10 was found to be predictive for the course of the disease in COPD, in particular mortality. The fact that Pi10 was lower in patients with severe COPD receiving triple therapy might hint toward additional effects of this functional therapy on airway remodeling. REGISTRATION: ClinicalTrials.gov, Identifier: NCT01245933.