Capnocytophaga canimorsus Septicemia With Sepsis-Induced Coagulopathy and Endocarditis.

Capnocytophaga canimorsus is a rare cause of serious infections with a high mortality of 10% to 30%. It is usually found in the oral cavity of cats and dogs and can cause severe sepsis in immunocompromised patients. An 81-year-old female Caucasian patient presented with C. canimorsus sepsis after a dog bite in her finger three days before presentation to our emergency department. She initially was presented to us with sepsis, thrombopenia, and schistocytes in her laboratory findings, suggesting the differential diagnoses of the multiple subtypes of thrombotic microangiopathy. She was admitted to the medical intensive care unit of the University Hospital of Saarland because of septic shock with circulatory insufficiency. The patient received plasmapheresis, antibiotics, and dialysis, under which she improved significantly. The fingertip of the affected finger developed necrosis and had to be amputated. Furthermore, the patient was diagnosed with a mitral valve endocarditis, a very rare complication of C. canimorsus infection. It was treated conservatively with antibiotics and was no longer detectable 8 weeks after the diagnosis. Surgical intervention was not needed. The case describes well that it is still difficult to distinguish between thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and sepsis-induced coagulopathy (SIC), especially in the early phases of acute disease, especially in C. canimorsus-induced sepsis.

Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics.

The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies.

Untreated pulmonary sequestration with recurrent superinfection -supporting COPD development in a 42 year old male patient.

BACKGROUND: Pulmonary sequestration is a congenital malformation in which nonfunctional lung tissue develops without connection to the bronchial system. The main complication is the occurrence of recurrent pneumonia. CASE PRESENTATION: We describe the case of a patient who was incidentally diagnosed with PS as part of the diagnostic algorithm for community-acquired pneumonia. Due to the relatively late diagnosis, the recurrent bronchopulmonary was conducive to the development of COPD and pulmonary emphysema. For prognostic reasons, surgical resection was performed by posterolateral thoracotomy. CONCLUSIONS: Although cigarette smoking is the main risk factor for developing COPD, recurring lung infections may have a synergistic effect. Sometimes recurrent infections are caused by a congenital malformation. Especially in adults who have had recurrent pneumonia since childhood.

Expiratory Venous Volume and Arterial Tortuosity are Associated with Disease Severity and Mortality Risk in Patients with COPD: Results from COSYCONET.

Purpose: The aim of this study was to evaluate the association between computed tomography (CT) quantitative pulmonary vessel morphology and lung function, disease severity, and mortality risk in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Participants of the prospective nationwide COSYCONET cohort study with paired inspiratory-expiratory CT were included. Fully automatic software, developed in-house, segmented arterial and venous pulmonary vessels and quantified volume and tortuosity on inspiratory and expiratory scans. The association between vessel volume normalised to lung volume and tortuosity versus lung function (forced expiratory volume in 1 sec [FEV1]), air trapping (residual volume to total lung capacity ratio [RV/TLC]), transfer factor for carbon monoxide (TLCO), disease severity in terms of Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D, and mortality were analysed by linear, logistic or Cox proportional hazard regression. Results: Complete data were available from 138 patients (39% female, mean age 65 years). FEV1, RV/TLC and TLCO, all as % predicted, were significantly (p < 0.05 each) associated with expiratory vessel characteristics, predominantly venous volume and arterial tortuosity. Associations with inspiratory vessel characteristics were absent or negligible. The patterns were similar for relationships between GOLD D and mortality with vessel characteristics. Expiratory venous volume was an independent predictor of mortality, in addition to FEV1. Conclusion: By using automated software in patients with COPD, clinically relevant information on pulmonary vasculature can be extracted from expiratory CT scans (although not inspiratory scans); in particular, expiratory pulmonary venous volume predicted mortality. Trial Registration: NCT01245933.

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.

Characterization and Mortality Risk of Impaired Left Ventricular Filling in COPD.

BACKGROUND: In COPD, impaired left ventricular (LV) filling might be associated with coexisting HFpEF or due to reduced pulmonary venous return indicated by small LV size. We investigate the all-cause mortality associated with small LV or HFpEF and clinical features discriminating between both patterns of impaired LV filling. METHODS: We performed transthoracic echocardiography (TTE) in patients with stable COPD from the COSYCONET cohort to define small LV as LVEDD below the normal range and HFpEF features according to recommendations of the European Society of Cardiology. We assessed the E/A and E/e' ratios, NT-pro-BNP, hs-Troponin I, FEV1, RV, DLCo, and discriminated patients with small LV from those with HFpEF features or no relevant cardiac dysfunction as per TTE (normalTTE). The primary outcome was all-cause mortality after four and a half year. RESULTS: In 1752 patients with COPD, the frequency of small LV, HFpEF-features, and normalTTE was 8%, 16%, and 45%, respectively. Patients with small LV or HFpEF features had higher all-cause mortality rates than patients with normalTTE, HR: 2.75 (95% CI: [1.54 - 4.89]) and 2.16 (95% CI: [1.30 - 3.61]), respectively. Small LV remained an independent predictor of all-cause mortality after adjusting for confounders including exacerbation frequency and measures of RV, DLCo, or FEV1. Compared to normalTTE, patients with small LV had reduced LV filling, as indicated by lowered E/A. Yet in contrast to patients with HFpEF-features, patients with small LV had normal LV filling pressure (E/e') and lower levels of NT-pro-BNP and hs-Troponin I. CONCLUSION: In COPD, both small LV and HFpEF-features are associated with increased all-cause mortality and represent two distinct patterns of impaired LV filling This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

An easy-to-perform protocol for culturing primary murine lung tumor cells as organoids.

Cancer research involves significant animal consumption and suffering. Tumor cells can be differentiated in vitro into three-dimensional organoids that resemble the primary tumor. In basic cancer research, however, tumor organoids are usually only used alongside animal experiments. We have established an easy-to-perform protocol that allows to culture KRAS-driven lung tumor cells as organoids for extended periods of time. Like the corresponding tumors in mice, the organoids produce surfactant protein C but no markers of airway epithelial cells (e.g. SCGB1A1, KRT5). The organoids can be passaged as single cell suspensions. Our organoid model contributes to replace animal experiments with cell culture systems and can be used for drug testing or functional studies in cancer research.

Carbon Dioxide Targets in Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

Target values for arterial carbon dioxide tension (PaCO2) in extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) are unknown. We hypothesized that lower PaCO2 values on ECMO would be associated with lighter sedation. We used data from two independent patient cohorts with ARDS spending 1,177 days (discovery cohort, 69 patients) and 516 days (validation cohort, 70 patients) on ECMO and evaluated the associations between daily PaCO2, pH, and bicarbonate (HCO3) with sedation. Median PaCO2 was 41 (interquartile range [IQR] = 37-46) mm Hg and 41 (IQR = 37-45) mm Hg in the discovery and the validation cohort, respectively. Lower PaCO2 and higher pH but not bicarbonate (HCO3) served as significant predictors for reaching a Richmond Agitation Sedation Scale (RASS) target range of -2 to +1 (lightly sedated to restless). After multivariable adjustment for mortality, tracheostomy, prone positioning, vasoactive inotropic score, Simplified Acute Physiology Score (SAPS) II or Sequential Organ Failure Assessment (SOFA) Score and day on ECMO, only PaCO2 remained significantly associated with the RASS target range (adjusted odds ratio 1.1 [95% confidence interval (CI) = 1.01-1.21], p = 0.032 and 1.29 [95% CI = 1.1-1.51], p = 0.001 per mm Hg decrease in PaCO2 for the discovery and the validation cohort, respectively). A PaCO2 ≤40 mm Hg, as determined by the concordance probability method, was associated with a significantly increased probability of a sedation level within the RASS target range in both patient cohorts (adjusted odds ratio = 2.92 [95% CI = 1.17-7.24], p = 0.021 and 6.82 [95% CI = 1.50-31.0], p = 0.013 for the discovery and the validation cohort, respectively).

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.

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.

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.