Body composition after endoscopic lung volume reduction with endobronchial valves: A prospective study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and emphysema experience malnutrition and pulmonary cachexia. Endoscopic lung volume reduction (ELVR) with endobronchial valves has not only improved lung function, exercise capacity, and quality of life, but also influenced body weight. Only a few data are available on body composition changes after ELVR. METHODS: This single-center prospective study of patients with advanced COPD investigates body composition before and after endoscopic valve treatment using multifrequency bioelectrical impedance analysis (BIA). The following parameters were evaluated in addition to clinical data and routine tests: body weight, body mass index (BMI), basal metabolic rate, total body water, body fat, cell percentage, phase angle, intracellular water (ICW), extracellular water (ECW), extracellular mass (ECM), body cell mas (BCM), lean body mass (LBM = ECM + BCM) and fat-free mass index. RESULTS: A total of 23 patients (mean emphysema index 37.2 ± 7.5 %, BMI 23.4 ± 4.3 kg/m²) experienced improvements in lung function and exercise capacity with ELVR. Complete lobar atelectasis was achieved in 39.1% of participants. A non-statistically significant increase in body weight and BMI was observed after ELVR (p = 0.111 and p = 0.102). BIA measurement revealed a worsening of phase angle, cell percentage and ECM/BCM and thus of body composition, but without statistical significance. This is mainly due to a statistically significant increase in ECM, ECW, and ICW (all p < 0.001). CONCLUSION: ELVR demonstrated no beneficial changes in body composition, although patients tend to gain weight. A larger cohort is warranted to confirm these findings. .

Design of the multicentre randomised controlled BENTO trial to demonstrate patient-relevant benefit of bronchoscopic lung volume reduction using thermal vapour ablation in the German healthcare system for patients with upper lobe emphysema: a study protocol.

INTRODUCTION: Application of vapour ablation as a novel approach to lung volume reduction has positive effects in patients with severe emphysema. The BENTO study is a randomised, controlled, open, multicentre trial, to assess the effects of bronchoscopic thermal vapour ablation (BTVA) in the German healthcare system. METHODS AND ANALYSIS: Patients with bilateral heterogeneous emphysema of the upper lobes in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3/4 will be enrolled in this trial and will receive either standard medical management alone (according to GOLD guidelines) or BTVA treatment with the InterVapor system together with standard medical management. Patients will be randomised in a 2:1 ratio (treatment group:control group). A total of 224 patients will be enrolled at 15 study sites. The primary endpoint is the change in patient-reported disease-specific quality of life, as measured by the St George's Respiratory Questionnaire for chronic obstructive pulmonary disease patients between randomisation and the 9-month follow-up visit. Secondary endpoints include adverse events, mortality, vital status, changes in lung function parameters, exercise capacity and other efficacy measures at 3, 9 and 12 months.The BENTO trial was commissioned by the German Federal Joint Committee, to demonstrate that this approach is an efficient and safe treatment option in the German healthcare system. ETHICS AND DISSEMINATION: The protocol has been approved by the lead ethics committee in Germany (Ethics Committee of the Medical Faculty of Heidelberg) and until present also by the following ethics committees: Ethics Committee of the Medical Faculty of Duisburg-Essen, Ethics Committee of the Medical Faculty of Martin-Luther-University Halle-Wittenberg, Ethics Committee of the State Medical Association of Hessen, Ethics Commission of the State Office for Health and Social Affairs of the State of Berlin, Ethics Committee of the Medical Faculty of Greifswald. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05717192.

Analysis of body composition with bioelectrical impedance analysis in patients with severe COPD and pulmonary emphysema.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from cachexia and malnutrition. Less is known about body composition and nutritional behaviour in patients with advanced COPD and pulmonary emphysema. METHODS: We performed a single-center prospective analysis of patients with COPD GOLD III/IV. Metabolic parameters, dietary and exercise behavior, lung function, exercise capacity and body composition by bioelectrical impedance analysis (BIA) were analyzed. Patients with severe emphysema (emphysema index [EI] >20%) were compared to patients with mild emphysema (EI ≤ 20%). RESULTS: A total of 121 patients (45.5% female, mean age 64.8 ± 8.1 years, mean FEV1 31.0 ± 8.6%, mean RV 234.7 ± 50.6%) were analyzed, of whom 14.1% were underweight. Only 5% of the patients substituted protein and only about 1/3 performed regular exercise training. BIA showed an unfavourable body composition: body fat ↑, ECM/BCM-index ↑, phase angle ↓ (5.0 ± 0.9°), cell percentage ↓, FFMI (fat-free mass index) ↓. The 94 patients with severe emphysema (mean EI 36.6 ± 8.5%) had lower body-mass-index (22.8 ± 4.3 vs. 31.1 ± 5.8 kg/m2, p < 0.001), FFMI, body weight and body fat, but did not differ significantly in the quality of body composition (e.g. phase angle). Their lipid and glucose metabolism were even better than in mild emphysema patients. CONCLUSION: The finding of significantly lower BMI but similar body composition and better metabolic status in severe emphysema patients needs further investigation. However, it should not distract from the necessity to implement dietary and exercise recommendations for advanced COPD patients.

Utility of rehabilitation prior to bronchoscopic lung volume reduction: post hoc analysis of the VENT trial.

Background and objective: Rehabilitation programmes are a valuable treatment modality for patients with COPD to increase exercise capacity and quality of life. The utility of pulmonary rehabilitation prior to bronchoscopic lung volume reduction (BLVR) is unclear. Methods: We performed a post hoc analysis of the Valve for Emphysema Palliation Trial (VENT) trial, the first multicentre randomised trial comparing the safety and efficacy of BLVR. Patients completed a pulmonary rehabilitation programme prior to BLVR over 6-10 weeks and maintained by daily practice, consisting of endurance training, strength training and upper/lower limb exercise. Lung function and exercise parameters (6-min walk distance (6MWD)) were assessed before and after rehabilitation and we tried to identify predictors for pulmonary rehabilitation benefit. Results: Lung function and exercise capacity of 403 patients (mean±sd age 63.3±7.4 years, 37.5% female, mean±sd forced expiratory volume in 1 s 30.1±7.6 L) were analysed. Exercise capacity significantly improved from 331.6±98.8 m to 345.6±95.3 m (p<0.001) in 6-min walk testing (6MWT), with 40.3% showing clinically meaningful improvements. Patients also experienced less dyspnoea after 6MWT, while pulmonary function parameters did not change significantly overall. Patients with lower exercise capacity at screening (6MWD <250 m) benefited more from pulmonary rehabilitation. The indication and prerequisites for BLVR were still present in all patients after pulmonary rehabilitation. Conclusion: The national mandatory requirements for rehabilitation prior to BLVR, which apply to all COPD patients, should be reconsidered and specified for COPD patients who really benefit.

Severe chronic obstructive pulmonary disease is associated with reduced oral health conditions.

OBJECTIVES: This study aimed to investigate the association of explicitly severe chronic obstructive pulmonary disease (COPD) with oral conditions considering in-depth shared risk factors. METHODS: A case-control study was conducted with 104 participants, 52 with severe COPD and 52 matched controls without COPD. Dental and periodontal status were clinically assessed and oral health-related quality of life (OHRQoL) by OHIP-G14-questionnaire. RESULTS: Between COPD- and control-group, there were no statistically significant differences regarding age (66.02 ± 7.30), sex (female: 52 [50%]), smoking history (44.69 ± 23.23 pack years) and number of systemic diseases (2.60 ± 1.38). COPD patients demonstrated significantly fewer remaining teeth (12.58 ± 9.67 vs. 18.85 ± 6.24, p < 0.001) besides higher DMFT (decayed, missing and filled teeth) index (21.12 ± 5.83 vs. 19.10 ± 3.91, p = 0.036). They had significantly greater probing pocket depths (PPD: 3.24 mm ± 0.71 mm vs. 2.7 mm ± 0.37 mm, p < 0.001) and bleeding on probing (BOP: 34.52% ± 22.03% vs. 22.85% ± 17.94%, p = 0.003) compared to controls, but showed no significant difference in clinical attachment level or staging of periodontitis. The OHIP-G14 sum score was significantly higher in COPD patients (7.40 ± 7.28 vs. 3.63 ± 4.85, p = 0.002). Common risk factors such as educational status, physical activity, dentist visit frequency, oral hygiene regimens and dietary habits were less favourable in patients with COPD. CONCLUSIONS: COPD was significantly associated with higher tooth loss, PPD, BOP and DMFT besides lower OHRQoL.

Endobronchial lung volume reduction with valves reduces exacerbations in severe emphysema patients.

BACKGROUND AND OBJECTIVE: Exacerbations drive the progression of chronic obstructive pulmonary disease (COPD). Endoscopic lung volume reduction (ELVR) with valves is an established treatment option for patients with severe emphysema. Post-interventional exacerbations are observed in 8-17% of cases. Whether the exacerbation rate changes in the medium term after ELVR, is not known. METHODS: This is a single-center retrospective analysis of severe emphysema patients with endobronchial valve implantation. The number of exacerbations before and after ELVR was compared, including lung function parameters, exercise capacity and degree of lung volume reduction. The primary endpoint of the study was the number of exacerbations one year after ELVR compared to one year before ELVR. RESULTS: 129 patients (mean age 64.1 ± 7.7 years, 57% female, mean FEV1 0.8 ± 0.2 l, mean RV 243.4 ± 54.9 %) with ELVR in the years 2016-2019 and complete exacerbation history were analyzed. Patients experienced a mean of 2.5 ± 2.2 moderate and severe exacerbations in the year before ELVR. The number of exacerbations decreased significantly to 1.8 ± 2.2 exacerbations in the first year after ELVR (p = 0.009). The decrease in exacerbation rate was associated with the development of complete lobar atelectasis (r = 0.228. p = 0.009). Accordingly, in 41 patients with complete lobar atelectasis, the decrease in exacerbation rate was higher from 2.8 ± 2.0 to 1.4 ± 1.8 exacerbations (p < 0.001). CONCLUSIONS: ELVR with valves appears promising to reduce the exacerbation rate in COPD patients, especially when the full treatment benefit of complete lobar atelectasis is achieved.

Women in Interventional Pulmonology: Results from a Worldwide Survey.

BACKGROUND AND OBJECTIVES: Gender inequality in medicine remains an issue. Despite the increasing proportion of female physicians, women still appear underrepresented in interventional pulmonology (IP) careers. To date, no data are available on the gender distribution in IP. METHOD: An online survey was sent to pulmonary physicians internationally between July and December 2022. The survey included questions on gender diversity in the pulmonology departments, such as the proportion of male, female, and gender diverse physicians performing bronchoscopy, career progression, and social life. RESULTS: Responses from 92 physicians (mean age 45 ± 10 years) from 47 hospitals across 17 countries were analysed, of whom 52% were women. Overall, 79% of the respondents were pulmonologists and 83% perform bronchoscopy. Although men continue to dominate bronchoscopy (65 vs. 43%) and are more likely to be involved in research (89 vs. 77%), the observed difference is statistically not significant (p = 0.135 and p = 0.281). Leading positions are held by 60% of male respondents and 23% of female respondents (p = 0.002). Men are also more often reported to have academic awards. Discrimination based on gender was reported by 5.3% of all men and 26.8% of all women (p = 0.023). CONCLUSIONS: Men and women are almost equally involved in IP, especially in female-led bronchoscopy units. However, leading positions and academic awards are still predominantly held by men.

Endobronchial Valve Replacements in Patients with Advanced Emphysema After Endoscopic Lung Volume Reduction.

Purpose: Up to 41% of patients with endobronchial valve implantation need revision bronchoscopies and valve replacements most likely due to valve dysfunction or lack of benefit. So far, no data is available whether valve replacements lead to the desired lobar volume reduction and therapy benefit. Patients and Methods: We conducted a single-center retrospective analysis of patients with endobronchial valve implantation and at least one valve replacement. Indications and number of revision bronchoscopies and valve replacements were evaluated. Therapy benefit regarding lung function and exercise capacity as well as development of complete lobar atelectasis was investigated and possible predictors identified. Results: We identified 73 patients with 1-12 revision bronchoscopies and 1-5 valve replacements. The main indication for revision bronchoscopy in this group was lack of therapy benefit (44.2%). Lung function and exercise capacity showed improvements in about one-third of patients even years after the initial implantation. A total of 26% of all patients showed a complete lobar atelectasis at the end of the observation period, 56.2% had developed lung volume reduction. The logistic regression revealed the development of a previous complete lobar atelectasis as predictor for a complete lobar atelectasis at final follow-up. Oral cortisone long-term therapy was also shown as predictive factor. The probability for a final complete lobar atelectasis was 69.2% if a lobar atelectasis had developed before. Conclusion: Valve replacements are more likely to be beneficial in patients who develop a re-aeration of a previous lobar atelectasis following valve implantation. Every decision for revision bronchoscopy must be taken carefully.

Characterization of three new SERPINA1 variants PiQ0Heidelberg II, PiQ0Heidelberg III and PiQ0Heidelberg IV in patients with severe alpha-1 antitrypsin deficiency.

Background: The clinical and molecular characteristics of three patients with previously unreported SERPINA1 mutations associated with severe alpha-1 antitrypsin deficiency (AATD) are described. The pathophysiology of the chronic obstructive pulmonary disease (COPD) present in these patients was characterized through clinical, biochemical, and genetic examinations. Case presentations: Case 1: A 73-year-old male with bilateral centri-to panlobular emphysema and multiple increasing ventrobasal bullae and incomplete fissures, COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade III B), progressive dyspnea on exertion (DOE), AAT level of 0.1-0.2 g/L. Genetic testing revealed a unique SERPINA1 mutation: Pi*Z/c.1072C > T. This allele was designated PiQ0Heidelberg II. Case 2: A 47-year-old male with severely heterogenous centri-to panlobular emphysema concentrated in the lower lobes, COPD GOLD IV D with progressive DOE, AAT <0.1 g/L. He also had a unique Pi*Z/c.10del mutation in SERPINA1. This allele was named PiQ0Heidelberg III. Case 3: A 58-year-old female with basally accentuated panlobular emphysema, GOLD II B COPD, progressive DOE. AAT 0.1 g/L. Genetic analysis revealed Pi*Z/c.-5+1G > A and c.-472G > A mutations in SERPINA1. This variant allele was named PiQ0Heidelberg IV. Conclusions: Each of these patients had a unique and previously unreported SERPINA1 mutation. In two cases, AATD and a history of smoking led to severe lung disease. In the third case, timely diagnosis, and institution of AAT replacement stabilized lung function. Wider screening of COPD patients for AATD could lead to faster diagnosis and earlier treatment of AATD patients with AATD which could slow or prevent progression of their disease.

Bronchoscopic Measurement of Collateral Ventilation: State of the Art.

Endoscopic lung volume reduction procedure with valves is a well-studied treatment option for advanced lung emphysema to target lung hyperinflation in carefully selected patients with COPD. Before valve implantation, collateral ventilation (CV) of the target lobe needs to be assessed to obtain an optimal treatment effect. The analysis of CV according to current standards occurs via an in vivo assessment with the Chartis®system (PulmonX Inc., Redwood City, CA, USA) and a computed tomography (CT) scan of the thorax with interlobar fissure analysis. The focus of this review is to provide detailed information about the Chartis®procedure and interpretation of Chartis® phenotypes. As a main tool in the assessment of CV and being a safe procedure, the Chartis® assessment should be performed by default to confirm interlobar fissure analysis in most emphysema patients. Based on the obtained results, lung volume reduction therapy options should be discussed in an interdisciplinary emphysema conference.

Augmentation therapy with human alpha-1-proteinase inhibitor reduces exacerbations in patient with bronchiectasis and alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency (AATD) is a rare cause of noncystic fibrosis (CF) bronchiectasis. The benefits of augmentation therapy in patients with chronic obstructive pulmonary disease (COPD) and pulmonary emphysema are well established. The role of augmentation therapy in AATD bronchiectasis in patients without pulmonary emphysema is not clear. We present the case of a 53-year-old woman (never smoker) who presented with increased susceptibility to infection, productive cough, and intermittent hemoptysis. Pulmonary function testing revealed restrictive impairment [VC 2,7 l (83% of pred.), FEV1 2,3 l (86% of pred.)]. A CT scan of the chest showed marked basal bronchiectasis with mucoid impaction, surrounding consolidation, and no emphysema. Despite frequent use of inhalation therapy, a satisfactory control of symptoms and exacerbations was not achieved. In the course of extended diagnostics regarding the genesis of bronchiectasis, a reduced alpha-1-antitrypsin (AAT) serum level was detected, and a genetic test revealed a homozygous Pi*ZZ genotype. We started augmentation therapy with AAT (Respreeza®, CLS Behring) at the dose of 60 mg/kg per week; the therapy was well tolerated by the patient, and she reported clinical improvement with a reduction in exacerbation frequency. AAT is a serine protease inhibitor and plays a major role in regulating inflammatory activities, in particular by inhibiting neutrophil elastase (NE). The present case illustrates the positive effect of augmentation therapy, including patients without airway obstruction. Among other causes, AATD should be considered as a possible cause of bronchiectasis, and the effects of augmentation therapy for this indication need to be prospectively studied.

Optimization of Mechanosensitive Cross-Talk between Matrix Stiffness and Protein Density: Independent Matrix Properties Regulate Spreading Dynamics of Myocytes.

Cells actively sense differences in topology, matrix elasticity and protein composition of the extracellular microenvironment and adapt their function and morphology. In this study, we focus on the cross-talk between matrix stiffness and protein coating density that regulates morphology and proliferation dynamics of single myocytes. For this, C2C12 myocytes were monitored on L-DOPA functionalized hydrogels of 22 different elasticity and fibronectin density compositions. Static images were recorded and statistically analyzed to determine morphological differences and to identify the optimized extracellular matrix (ECM). Using that information, selected ECMs were used to study the dynamics before and after cell proliferation by statistical comparison of distinct cell states. We observed a fibronectin-density-independent increase of the projected cell area until 12 kPa. Additionally, changes in fibronectin density led to an area that was optimum at about 2.6 µg/cm2, which was confirmed by independent F-actin analysis, revealing a maximum actin-filament-to-cell-area ratio of 7.5%. Proliferation evaluation showed an opposite correlation between cell spreading duration and speed to matrix elasticity and protein density, which did not affect cell-cycle duration. In summary, we identified an optimized ECM composition and found that independent matrix properties regulate distinct cell characteristics.

Interaction of Nitrate Assimilation and Photorespiration at Elevated CO2.

It has been shown repeatedly that exposure to elevated atmospheric CO2 causes an increased C/N ratio of plant biomass that could result from either increased carbon or - in relation to C acquisition - reduced nitrogen assimilation. Possible reasons for diminished nitrogen assimilation are controversial, but an impact of reduced photorespiration at elevated CO2 has frequently been implied. Using a mutant defective in peroxisomal hydroxy-pyruvate reductase (hpr1-1) that is hampered in photorespiratory turnover, we show that indeed, photorespiration stimulates the glutamine-synthetase 2 (GS) / glutamine-oxoglutarate-aminotransferase (GOGAT) cycle, which channels ammonia into amino acid synthesis. However, mathematical flux simulations demonstrated that nitrate assimilation was not reduced at elevated CO2, pointing to a dilution of nitrogen containing compounds by assimilated carbon at elevated CO2. The massive growth reduction in the hpr1-1 mutant does not appear to result from nitrogen starvation. Model simulations yield evidence for a loss of cellular energy that is consumed in supporting high flux through the GS/GOGAT cycle that results from inefficient removal of photorespiratory intermediates. This causes a futile cycling of glycolate and hydroxy-pyruvate. In addition to that, accumulation of serine and glycine as well as carboxylates in the mutant creates a metabolic imbalance that could contribute to growth reduction.

Endoscopic Options for Moderate COPD, Chronic Bronchitis, and Uncontrolled Asthma.

Until now, interventional therapies for patients with chronic obstructive pulmonary disease have been available in the form of lung volume reduction procedures as end-stage options. Currently, the range of indications is expanding to include earlier stages of the diseases. Lung denervation is available for moderate COPD, and patients with chronic bronchitis are being evaluated for endoscopic goblet cell ablation. Rheoplasty, metered spray cryo technique, and Karakoca resector balloon are used for this indication. But also, for patients with severe uncontrolled asthma, several techniques are available today. In addition to thermoplasty as a long-proven procedure, new and currently under investigation is the targeted lung denervation.Most of these techniques are currently being tested in large pivotal trials and it will soon become clear in which phenotype which technique will be used in the different forms and stages of obstructive diseases. The current paper presents the techniques and the currently available literature.

Inhaled Steroids, Sex and Emphysema Index - Clinical Parameters with Impact on the Effectiveness of Valve Implantation in Patients with Severe Emphysema.

Aims and Objectives: Many patients with chronic obstructive lung disease suffer from emphysema. Valve implantation may be a reasonable method in patients presenting advanced emphysema and absent interlobar collateral ventilation (CV). However, other clinical parameters influencing the effectiveness of endoscopic lung volume reduction (ELVR) are not well known. Methods: COPD patients with advanced emphysema who received valve implantation in 2016 were retrospectively analyzed. The following characteristics were collected prior to valve implantation: age, sex, body mass index, presence of allergies, use of inhaled corticosteroids (ICS), lung function parameters, diffusion capacity, 6-minute walk distance (6-MWD), blood gases, COHb, smoking history, and emphysema index (quantitative multi-detector computed tomography). Three months following valve implantation, lung function parameters, diffusion capacity, 6-MWD and blood gases were measured. In this analysis, we evaluated the impact of these variables on an increase in FEV1 and 6-MWT as well as a decrease in RV three months after valve implantation. Results: Overall, 77 COPD patients (57% male, mean age 66, mean FEV1 32%, mean RV 259%) who underwent valve therapy were enrolled. At 3-month follow-up, patients experienced a mean FEV1 increase of 0.09 ± 0.21 L, a mean RV decrease of 0.42 ± 1.80 L and a mean improvement of 8.3 ± 57 m in the 6-MWT. Overall, ICS, sex and emphysema index had an impact on the outcome following ELVR: ICS medication was associated with inferior FEV1 outcome. The higher the emphysema index, the less the RV reduction. Sex was a predictor for change of FEV1 (%), RV (L), and 6-MWT: male patients seem to benefit less than female patients from valve implantation. Conclusion: These findings suggest that ICS, emphysema index and sex are clinical parameters that may be associated with inferior outcome following ELVR. Further studies have to confirm these results to improve patient selection and clinical outcome of ELVR.

ERS International Congress 2021: highlights from the Clinical Techniques, Imaging and Endoscopy Assembly.

This article summarises the highlights from the European Respiratory Society's "Clinical techniques, imaging and endoscopy" Assembly 14 presented at the virtual 2021 European Respiratory Society International Congress. Cutting-edge innovative developments in both diagnostic approaches and therapeutic strategies in patients with lung cancer, interstitial lung disease, obstructive airway disorders and infectious diseases were presented on this year's interactive congress platform. In this article, the Assembly 14 subgroups summarise the key take home messages given new research outcomes and place them in the context of the current knowledge.

Differentiating COPD and asthma using quantitative CT imaging and machine learning.

BACKGROUND: There are similarities and differences between chronic obstructive pulmonary disease (COPD) and asthma patients in terms of computed tomography (CT) disease-related features. Our objective was to determine the optimal subset of CT imaging features for differentiating COPD and asthma using machine learning. METHODS: COPD and asthma patients were recruited from Heidelberg University Hospital (Heidelberg, Germany). CT was acquired and 93 features were extracted: percentage of low-attenuating area below -950 HU (LAA950), low-attenuation cluster (LAC) total hole count, estimated airway wall thickness for an idealised airway with an internal perimeter of 10 mm (Pi10), total airway count (TAC), as well as airway inner/outer perimeters/areas and wall thickness for each of five segmental airways, and the average of those five airways. Hybrid feature selection was used to select the optimum number of features, and support vector machine learning was used to classify COPD and asthma. RESULTS: 95 participants were included (n=48 COPD and n=47 asthma); there were no differences between COPD and asthma for age (p=0.25) or forced expiratory volume in 1 s (p=0.31). In a model including all CT features, the accuracy and F1 score were 80% and 81%, respectively. The top features were: LAA950, outer airway perimeter, inner airway perimeter, TAC, outer airway area RB1, inner airway area RB1 and LAC total hole count. In the model with only CT airway features, the accuracy and F1 score were 66% and 68%, respectively. The top features were: inner airway area RB1, outer airway area LB1, outer airway perimeter, inner airway perimeter, Pi10, TAC, airway wall thickness RB1 and TAC LB10. CONCLUSION: COPD and asthma can be differentiated using machine learning with moderate-to-high accuracy by a subset of only seven CT features.

Acclimation to elevated CO2 affects the C/N balance by reducing de novo N-assimilation.

Plants exposed to elevated atmospheric CO2 concentrations show an increased photosynthetic activity. However, after prolonged exposure, the activity declines. This acclimation to elevated CO2 is accompanied by a rise in the carbon-to-nitrogen ratio of the biomass. Hence, increased sugar accumulation and sequential downregulation of photosynthetic genes, as well as nitrogen depletion and reduced protein content, have been hypothesized as the cause of low photosynthetic performance. However, the reason for reduced nitrogen content in plants at high CO2 is unclear. Here, we show that reduced photorespiration at increased CO2 -to-O2 ratio leads to reduced de novo assimilation of nitrate, thus shifting the C/N balance. Metabolic modeling of acclimated and non-acclimated plants revealed the photorespiratory pathway to function as a sink for already assimilated nitrogen during the light period, providing carbon skeletons for de novo assimilation. At high CO2 , low photorespiratory activity resulted in diminished nitrogen assimilation and eventually resulted in reduced carbon assimilation. For the hpr1-1 mutant, defective in reduction of hydroxy-pyruvate, metabolic simulations show that turnover of photorespiratory metabolites is expanded into the night. Comparison of simulations for hpr1-1 with those for the wild type allowed investigating the effect of a perturbed photorespiration on N-assimilation.