Swarm Learning for decentralized and confidential clinical machine learning.

Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning-a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. METHODS: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. RESULTS: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively). CONCLUSIONS: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy.

Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with more than 200 entities and relevant differences in disease course and prognosis. Little data is available on hospitalisation patterns in ILD. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for hospitalisations. Reasons for hospitalisation were classified as all cause, ILD-related and respiratory hospitalisations, and patients were analysed for frequency of hospitalisations, time to first non-elective hospitalisation, mortality and progression-free survival. Additionally, the risk for hospitalisation according to GAP index and ILD subtype was calculated by Cox proportional-hazard models as well as influencing factors on prediction of hospitalisation by logistic regression with forward selection. RESULTS: In total, 601 patients were included. 1210 hospitalisations were recorded during the 6 months prior to registry inclusion until the last study visit. 800 (66.1%) were ILD-related, 59.3% of admissions were registered in the first year after inclusion. Mortality was associated with all cause, ILD-related and respiratory-related hospitalisation. Risk factors for hospitalisation were advanced disease (GAP Index stages II and III) and CTD (connective tissue disease)-ILDs. All cause hospitalisations were associated with pulmonary hypertension (OR 2.53, p = 0.005). ILD-related hospitalisations were associated with unclassifiable ILD and concomitant emphysema (OR = 2.133, p = 0.001) as well as with other granulomatous ILDs and a positive smoking status (OR = 3.082, p = 0.005). CONCLUSION: Our results represent a crucial contribution in understanding predisposing factors for hospitalisation in ILD and its major impact on mortality. Further studies to characterize the most vulnerable patient group as well as approaches to prevent hospitalisations are warranted.

Disease trajectories in interstitial lung diseases - data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5-10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression. RESULTS: Within the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001). CONCLUSION: Disease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful.

Assessing sleep-related breathing disorders among newly diagnosed rheumatoid and psoriatic arthritis patients: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to determine the prevalence and risk factors for sleep-related breathing disorders (SRBD) in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to develop a screening algorithm for early detection. METHODS: We evaluated newly diagnosed RA or PsA patients using the Epworth Sleepiness Scale (ESS) questionnaire, cardiorespiratory polygraphy (RPG), and clinical and laboratory assessments. Sleep apnea syndrome (SAS) was diagnosed based on pathological RPG findings excessive daytime sleepiness, defined as ESS score above 10. RESULTS: The study included 39 patients (22 RA, 17 PsA) and 23 controls. In RPG, SRBD was identified in 38.5% of arthritis patients compared to 39.1% of controls (p = 1.00), with male gender (p = .004) and age (p < .001) identified as risk factors. Excessive daytime sleepiness was noted in 36.4% of RA patients, 17.6% of PsA patients, and 21.7% of controls. Of the 24 patients diagnosed with SRBD, 41.6% met the criteria for SAS. SAS prevalence was 31.8% among RA patients, 0% in PsA patients, and 13% in controls. A significant association was observed between excessive daytime sleepiness and SRBD (p = .036). CONCLUSION: Our findings reveal a high prevalence of SRBD in newly diagnosed, untreated RA and PsA patients in ESS and RPG, with excessive daytime sleepiness being a reliable predictor of SRBD. Patients with RA exhibited a higher predisposition to SAS. We therefore suggest incorporating ESS and RPG as screening tools in RA or PsA for early detection and management of SRBD.

Influence of pseudoxanthoma elasticum on the lipid profile and prognostic implications.

Background: Pseudoxanthoma elasticum (PXE) is a rare, inherited disease characterised by specific skin lesions, progressive loss of vision and early onset atherosclerosis. Atherosclerosis in PXE leads to an increased rate of vascular occlusion and severe intermittent claudication. Although genetically determined, the individual course of PXE is highly variable. Up to now, there is no sufficient parameter to identify individuals at risk of rapid disease progression. This present study focused the lipid profile of patients with PXE and its possible influence on the clinical severity of peripheral artery disease (PAD). Patients and methods: 112 patients with PXE were retrospectively screened. Patients without a complete lipid profile consisting of total cholesterol (TC), triglycerides (TGC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and Lipoprotein(a) (Lp[a]) where excluded as well as patients with already initiated lipid-lowering therapy. 52 patients met the inclusion criteria. An age-adjusted ordinal regression model was applied to determine the association of each lipid fraction with the severity of PAD assessed as Fontaine classification. Results: The lipid profile of patients with PXE was unremarkable (TGC: 135.8±105.8 mg/dl; TC: 172.5±44.4 mg/dl; HDL: 63.0±18.2 mg/dl; Lp[a]: 64.7±93.5 nmol/l). Ordinal regression showed a significant association of Lp(a) with the severity of PAD with an odds ratio of 1.01 (1.00-1.02; p = 0.004), whereas the other fractions of the lipid profile had no significant influence. Conclusions: This study provides the largest evaluation of blood lipids up to now and the first characterization of Lp(a) levels in patients with PXE. We were able to provide first evidence of a correlation between elevated levels of Lp(a) and the severity of PAD. The present results suggest that determination of Lp(a) in early stages of PXE could help to identify patients at risk of rapid disease progression and with the need of intensified walking exercise training.

[Allergic bronchopullmonary aspergillosis (ABPA) - an Update]. / Allergische bronchopulmonale Aspergillose (ABPA) ­ ein Update.

Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling. Symptoms are highly variable and rather non-specific, overlapping with those of the underlying primary disease. However, clearly defined diagnostic criteria exist, so that the diagnosis can be made relatively easily if one thinks of it. In therapy, systemic steroids and antifungals (mainly azoles) play the leading role. However, biologics have been gaining in importance in recent years, especially in cases of insufficient therapy response or occurrence of side effects to standard therapies, as well as an alternative in permanently steroid-dependent patients.

[Therapeutic Pathways in Sarcoidosis. A Position Paper of the German Society of Respiratory Medicine (DGP)]. / Therapie der Sarkoidose. Ein Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.

Cardiac autonomic dysfunction in adult congenital heart disease.

PURPOSE: Due to recent advances in diagnosis and treatment, the number of adults with congenital heart disease (ACHD) has substantially increased. This achievement is mitigated by rhythm disorders. Here, we sought to determine alterations in heart rate variability (HRV) and their prognostic value in ACHD. METHODS: Ninety seven ACHD patients (39.2 ± 14.1 years, 51.5% female) and 19 controls (39.7 ± 15.0 years, 47.4% female) underwent 24-h Holter monitoring. RESULTS: As compared to controls, ACHD patients offered a significantly higher burden of premature ventricular contractions (p = 0.02) and decreased HRV indices (natural logarithmic transformation of very low frequency (lnVLF): 7.46 ± 0.76 ms2 vs. 7.91 ± 0.92ms2, p = 0.03; natural logarithmic transformation of low frequency (lnLF): 6.39 ± 0.95ms2 vs. 7.01 ± 1.07ms2, p = 0.01; natural logarithmic transformation of the ratio of low to high frequency spectra (lnLF/HF): 0.81 ± 0.74 vs. 1.17 ± 0.51, p = 0.04). No differences in HRV measures were observed across ACHD lesion groups. NT-proBNP levels were significantly related to both time and frequency domain indices (natural logarithmic transformation of the standard deviation of NN intervals (lnSDNN): Spearman´s rho = -0.32, p = 0.001; natural logarithmic transformation of the standard deviation of the average NN intervals for each 5-min segment of a 24-h Holter monitoring (lnSDANN): Spearman´s rho: -0.33, p = 0.001; natural logarithmic transformation of the total power (lnTP): Spearman´s rho: -0.25, p = 0.01; lnVLF: Spearman´s rho: -0.33, p = 0.001; lnLF: Spearman´s rho: -0.35, p < 0.001; lnLF/HF: Spearman´s rho: -0.34, p = 0.001). After a mean follow-up of 3.9 ± 0.7 years, 8 patients died and 3 patients survived sudden cardiac death (SCD). Several HRV parameters were significantly higher in event-free ACHD patients than in those who died or survived SCD (natural logarithmic transformation of the average of the standard deviations of NN intervals for each 5-min segment of a 24-h Holter monitoring (lnASDNN): p = 0.04; lnPNN30: p = 0.04; lnVFL: p = 0.03; lnLF: p < 0.01). On univariate Cox regression analysis, the time domain indices lnSDNN, lnASDNN and lnPNN30, as well as the frequency domain parameters lnTP, lnVLF and lnLF were associated with death and survived cardiac arrest. CONCLUSION: ACHD is accompanied by HRV impairment that carries prognostic implications on ACHD mortality and survived SCD.

Prevalence of sleep-disordered breathing in patients with mitral regurgitation and the effect of mitral valve repair.

PURPOSE: The relationship between chronic heart failure and sleep-disordered breathing (SDB) has been frequently described. However, little is known about the association of mitral regurgitation (MR) and SDB or the impact of transcatheter mitral valve repair (TMVR) on SDB. Our aims were first to determine the prevalence of SDB in patients with MR, and second to determine the effect of TMVR on SDB. METHODS: Patients with MR being evaluated for TMVR at the University Hospital Bonn underwent polygraphy (PG) to determine the prevalence of SDB. After TMVR, a subset of patients was followed up with transthoracic echocardiography (TTE) and PG to evaluate the effect of TMVR on SDB. RESULTS: In 53 patients, mean age was 76.0 ± 8.5 years and 62% were male. Patients predominantly had more than moderate mitral regurgitation (94%). SDB was highly prevalent (68%) with predominantly central sleep apnoea (CSA, 67%). After TMVR in 15 patients, the apnoea/hypopnoea index (AHI) and central apnoea index (AI) were significantly reduced among patients with SDB (AHI - 8.0/h, p = 0.021; central AI - 6.9/h, p = 0.046). The left atrial volume index (LAVI) at baseline was significantly higher in patients with CSA than in patients with obstructive sleep apnoea (OSA) and was significantly reduced after TMVR (63.5 ml/m2 ± 27.2 vs. 38.3 ml/m2 ± 13.0; - 18.4 ml/m2, p = 0.027). CONCLUSION: SDB, especially CSA, is highly prevalent in patients with mitral regurgitation. In the follow-up cohort TMVR led to a significant reduction of the AHI, predominantly of central events. The findings of the study suggest that TMVR may be a suitable therapy not only for MR but also for the accompanying CSA. LAVI may be a useful indicator for CSA in patients with MR.

Preclinical atherosclerotic burden in carotid and lower extremity arteries in adults with congenital heart disease.

Background: Over 90% of patients with congenital heart defects now reach adulthood, due to significant medical advances in recent decades. With advancing age, the risk of acquired cardiovascular diseases increases in addition to the already existing risk due to the congenital defect. The aim of this study was to evaluate the prevalence of atherosclerotic lesions in carotid and lower extremity arteries in adults with congenital heart disease (ACHD). Patients and methods: A total number of 108 ACHD patients (40.6±15.0 years, 50.0% male) and 22 healthy controls (39.3±16.6 years, 40.9% male) were included in this prospective study and underwent a comprehensive angiological examination that included vascular strain analysis on the common carotid artery. Results were stratified by the underlying ACHD lesion groups: shunt lesions (n=26), left-sided obstructive lesions (n=29), right-sided lesions (n=26) and complex lesions (n=27). Results: Colour-coded duplex sonography revealed atherosclerotic lesions in lower extremity arteries in 19 ACHD patients (17.6%). This prevalence did not significantly differ from the one assessed in controls (13.6%, p=0.77). All cases were asymptomatic and therefore classified as Fontaine stage I. 20.4% of ACHD patients presented atherosclerotic lesions in extracranial carotid arteries; amongst controls, the corresponding proportion was 18.4% (p=1.00). No significant differences were observed in atherosclerotic burden in extracranial carotid and lower limb arteries across the four ACHD patient groups (p=0.67 and p=0.89, respectively). Vascular strain analysis revealed no differences between patients and controls. Though circumferential strain varied over ACHD groups (p<0.05), comparison of strain measurements across all specific underlying defect subgroups revealed no significant difference for any of the studied strain parameters. Conclusions: ACHD patients present an atherosclerotic burden in extracranial carotid and lower limb arteries and a vascular stiffness that is comparable to healthy controls.

High prevalence of peripheral and carotid artery disease in patients with interstitial lung diseases.

Background: Interstitial lung diseases (ILD) are a heterogenous group of diseases, which have pulmonary fibrosis, restrictive lung disease, and decreased diffusion capacity as a common final path. Premature death frequently results not from ILD itself but from comorbidities. Peripheral artery disease (PAD) is a common comorbid disease in different chronic lung diseases. The focus of the present study is to clarify the prevalence of PAD in ILD. Patients and methods: A total of 97 patients with ILD and 30 controls were included in the study. Patients with ILD were subdivided into two groups according to the progression of pulmonary fibrosis: progressive fibrosing and non-progressive fibrosing ILD (PF-ILD and nPF-ILD, respectively). All participants underwent standard angiological and pneumological diagnostic procedures including six-minute walking test, measurement of ankle-brachial-index, and colour-coded duplex sonography. Results: We observed no relevant differences in the baseline characteristics except age. Both, PF-ILD and nPF-ILD patients, presented with a highly increased incidence of atherosclerotic lesions compared to the control group (p<0.001). PAD was present in all patients with PF-ILD and in 73% of patients with nPF-ILD. These results were confirmed by age-adjusted regression analyses. Conclusions: The present results indicate that ILD is an independent risk factor for atherosclerosis. Patients with PF-ILD are more severely affected than nPF-ILD patients with age as a confounding variable. Atherogenesis in ILD may be mediated by increased cardiovascular risk, systemic inflammation and chronic hypoxemia.

[Haemoptysis]. / Hämoptysen.

Haemoptysis describes the expectoration of blood originating from the tracheobronchial tree and lung. Its presentation varies from mild to massive haemoptysis, the latter entailing the risk of asphyxia and thus requiring rapid intervention that spans multiple specialties.

Impact of short-term pausing of oral corticosteroids on blood eosinophil count in patients with severe asthma.

BACKGROUND: The peripheral blood eosinophil count (BEC) is a well-established and easily accessible biomarker for asthma patients and crucial for the therapeutic decision regarding monoclonal antibody (mAB) therapy. Oral corticosteroid therapy frequently hinders the correct evaluation of BEC in patients with severe asthma, but a discontinuation of such therapy frequently comes along with severe side effects. Therefore, we examined the effect of a short 24-hour pause of OCS treatment on BEC in patients with severe asthma and followed-up whether patients with a then increased eosinophil count benefited from mAB-therapy, as expected. METHODS: In this multicentre study we retrospectively included 24 patients with severe asthma and OCS therapy and determined their BEC count. Ten patients, where BEC count was obtained in the morning before taking medication (a de-facto 24-hour OCS pause), were assigned to group 1. Fourteen patients, where BEC was obtained after OCS tapering were assigned to group 2. Those who then received mAB treatment were followed up for treatment response (OCS dose, annual acute exacerbations, increase in forced expiratory volume in one second [FEV1] and asthma control test [ACT]) after ≥3 months. RESULTS: We included 24 patients with a median age of 60.5 [IQR: 17.3] years. Regarding all baseline characteristics except FEV1 (l), both groups did not differ significantly.Among all 24 patients, after pausing OCS therapy for 2 [5.5] days the BEC increased significantly from 125.0/µl [125] to 300/µl [232.5] (p<0.001). In both individual groups BEC increased significantly as well (150 [123] to 325 [305], p=0.005 and 70 [150] to 280 [255], p<0.001), with no significant difference for increase (BEC +170/µl [205.0] vs. +195 [222.5], p=0.886). Of all 24 patients, 13 (54.2%) reached eosinophil levels ≥300/µl, while 12 of them had not exceeded this threshold before.Subsequently, 20 patients (83.3%) received mAB-therapy with 55.5% demonstrating a good treatment response within 6 [1.5] months. The response rate in patients with BEC count ≥300/µl was even higher (75.0%). There was no difference in the treatment response rate between group 1 and 2 (p=0.092). CONCLUSION: After just a short 24-hour pause of OCS therapy it was possible to demask a relevant eosinophilia in asthma patients, without risking severe side effects. In this manner, we enabled the possibility of achieving successful targeted mAB-therapy, according to the patient's individual asthma phenotype.

[Criteria for evaluation of response to biologics in severe asthma - the Biologics Asthma Response Score (BARS)]. / Kriterien zur Evaluation des Ansprechens auf Biologika bei schwerem Asthma ­ der Biologics Asthma Response Score (BARS).

BACKGROUND: The introduction of monoclonal antibodies (biologics) has revolutionized the therapy of severe asthma. Even though there is a response in the majority of patients, the degree of response varies. To date criteria for assessment of response to biologics are not consistently defined. AIM: To define criteria for evaluation of response to biologics that are precise, simple and suitable for daily use in order to guide decision-making regarding continuation, switching or stopping of biological therapy. METHODS: 8 physicians with large experience in this indication, supported by a data-scientist, developed a consensus on criteria to evaluate response to biologics in patients with severe asthma. RESULT: We developed a combined score based on current literature, own experience and practicability. It uses the main criteria exacerbations, oral corticosteroid (OCS) therapy and asthma control (asthma control test, ACT). We defined thresholds for "good response", "response" and "insufficient response" rated with a score of "2", "1" and "0" respectively: annual exacerbations ("0 or reduction ≥ 75 %", reduction 50-74 %", "reductio  < 50 %"), daily OCS dose ("stopping or reduction ≥ 75 %", "reduction 50-74 %", "reduction < 50 %"), asthma control (ACT increase ≥ 6 or ≥ 3 with result ≥ 20", "ACT increase 3-5 with result < 20", "ACT increase < 3"). Additional individual criteria like lung function and comorbidities may be important for evaluation of response. We propose 3, 6 and 12 months timepoint for assessment of tolerability and response. Using the combined score, we developed a scheme to guide the decision whether switching the biologic should be considered. CONCLUSION: The Biologic Asthma Response Score (BARS) serves as objective and simple tool to evaluate response to biologic therapy using the three main criteria exacerbations, OCS use and asthma control. A validation of the score was initiated.

Criteria for evaluation of response to biologics in severe asthma - the Biologics Asthma Response Score (BARS).

BACKGROUND: The introduction of monoclonal antibodies (biologics) has revolutionized the therapy of severe asthma. Even though there is a response in the majority of patients, the degree of response varies. To date criteria for assessment of response to biologics are not consistently defined. AIM: To define criteria for evaluation of response to biologics that are precise, simple and suitable for daily use in order to guide decision-making regarding continuation, switching or stopping of biological therapy. METHODS: 8 physicians with large experience in this indication, supported by a data-scientist, developed a consensus on criteria to evaluate response to biologics in patients with severe asthma. RESULT: We developed a combined score based on current literature, own experience and practicability. It uses the main criteria exacerbations, oral corticosteroid (OCS) therapy and asthma control (asthma control test, ACT). We defined thresholds for "good response", "response" and "insufficient response" rated with a score of "2", "1" and "0" respectively: annual exacerbations ("0 or reduction ≥ 75 %", "reduction 50-74 %", "reductio < 50 %"), daily OCS dose ("stopping or reduction ≥ 75 %", "reduction 50-74 %", "reduction < 50 %"), asthma control ("ACT increase ≥ 6 or ≥ 3 with result ≥ 20", "ACT increase 3-5 with result < 20", "ACT increase < 3"). Additional individual criteria like lung function and comorbidities may be important for evaluation of response. We propose 3, 6 and 12 months timepoint for assessment of tolerability and response. Using the combined score, we developed a scheme to guide the decision whether switching the biologic should be considered. CONCLUSION: The Biologic Asthma Response Score (BARS) serves as objective and simple tool to evaluate response to biologic therapy using the three main criteria exacerbations, OCS use and asthma control. A validation of the score was initiated.

[Medication treatment in pulmonary arterial hypertension with comorbidities - Which phenotypes and points to consider]. / Medikamentöse Therapie der pulmonalarteriellen Hypertonie mit Komorbiditäten ­ Welche Phänotypen gibt es, was gibt es zu beachten?

Within the last decade, the age at diagnosis of patients with pulmonary arterial hypertension has increased, which led to a change of the clinical phenoype being associated with more comorbidities. Cluster analyses of registry data have identified cardiac, cardio-pulmonary and classical phenotypes of pulmonary arterial hypertension.Subgroup analyses of randomised controlled trials and registry data indicate, that in patients with pulmonary arterial hypertension and cardiac comorbidities, especially the left-heart phenotype, a closely supervised combination treatment may be considered. The 4-strata model may be used for monitoring and risk stratification in these patients. Individual treatment decisions should be made in the pulmonary hypertension centre. Factors such as hemodynamics, age, phenotype, number and severity of comorbidities, therapy response, adverse reactions and the wish of the patient should be considered.Prospective, randomized studies to assess the efficacy and safety profile of pulmonary arterial hypertension treatments are desirable. Patients with a mainly pulmonary phenotype (smoking, diffusion capacity of the lung < 45 % and/or lung parenchymal changes) may have less benefit of oral medication.

[Pulmonary hypertension associated with lung disease]. / Pulmonale Hypertonie assoziiert mit Lungenerkrankungen.

Lung diseases and hypoventilation syndromes are often associated with pulmonary hypertension (PH). In most cases, PH is not severe. This is defined hemodynamically by a mean pulmonary arterial pressure (PAPm) > 20 mmHg, a pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance of ≤ 5 Wood units (WU). Both the non-severe (PVR ≤ 5 WU) and much more the severe PH (PVR > 5 WU) have an unfavorable prognosis.If PH is suspected, it is recommended to primarily check whether risk factors for pulmonary arterial hypertension (PAH, group 1 PH) or chronic thromboembolic pulmonary hypertension (CTEPH, group 4 PH) are present. If risk factors are present or there is a suspicion of severe PH in lung patients, it is recommended that the patient should be presented to a PH outpatient clinic promptly.For patients with severe PH associated with lung diseases, personalized, individual therapy is recommended - if possible within the framework of therapy studies. Currently, a therapy attempt with PH specific drugs should only be considered in COPD patients if the associated PH is severe and a "pulmonary vascular" phenotype (severe precapillary PH, but typically only mild to moderate airway obstruction, no or mild hypercapnia and DLCO < 45 % of predicted value) is present. In patients with severe PH associated with interstitial lung disease phosphodiesterase-5-inhibitors may be considered in individual cases. Inhaled treprostinil may be considered also in non-severe PH in this patient population.

COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension.

BACKGROUND: Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum model to categorise risk as low, intermediate or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk. METHODS: We analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan-Meier analyses, log-rank testing and Cox proportional hazards models. RESULTS: Data from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the three-stratum model and in 49.2% with the four-stratum model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk. CONCLUSIONS: Modified risk stratification using a four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.