As-needed low-dose inhaled corticosteroid/formoterol therapy in patients with severe asthma included in the German Asthma Net cohort.

After the GINA update in 2019, the proportion of SMART therapy increased with evidence for better disease control in SMART patients compared to SABA alone https://bit.ly/3SSPX1C.

The role of coronary artery disease in lung transplantation: a propensity-matched analysis.

BACKGROUND AND AIMS: Candidate selection for lung transplantation (LuTx) is pivotal to ensure individual patient benefit as well as optimal donor organ allocation. The impact of coronary artery disease (CAD) on post-transplant outcomes remains controversial. We provide comprehensive data on the relevance of CAD for short- and long-term outcomes following LuTx and identify risk factors for mortality. METHODS: We retrospectively analyzed all adult patients (≥ 18 years) undergoing primary and isolated LuTx between January 2000 and August 2021 at the LMU University Hospital transplant center. Using 1:1 propensity score matching, 98 corresponding pairs of LuTx patients with and without relevant CAD were identified. RESULTS: Among 1,003 patients having undergone LuTx, 104 (10.4%) had relevant CAD at baseline. There were no significant differences in in-hospital mortality (8.2% vs. 8.2%, p > 0.999) as well as overall survival (HR 0.90, 95%CI [0.61, 1.32], p = 0.800) between matched CAD and non-CAD patients. Similarly, cardiovascular events such as myocardial infarction (7.1% CAD vs. 2.0% non-CAD, p = 0.170), revascularization by percutaneous coronary intervention (5.1% vs. 1.0%, p = 0.212), and stroke (2.0% vs. 6.1%, p = 0.279), did not differ statistically between both matched groups. 7.1% in the CAD group and 2.0% in the non-CAD group (p = 0.078) died from cardiovascular causes. Cox regression analysis identified age at transplantation (HR 1.02, 95%CI [1.01, 1.04], p < 0.001), elevated bilirubin (HR 1.33, 95%CI [1.15, 1.54], p < 0.001), obstructive lung disease (HR 1.43, 95%CI [1.01, 2.02], p = 0.041), decreased forced vital capacity (HR 0.99, 95%CI [0.99, 1.00], p = 0.042), necessity of reoperation (HR 3.51, 95%CI [2.97, 4.14], p < 0.001) and early transplantation time (HR 0.97, 95%CI [0.95, 0.99], p = 0.001) as risk factors for all-cause mortality, but not relevant CAD (HR 0.96, 95%CI [0.71, 1.29], p = 0.788). Double lung transplant was associated with lower all-cause mortality (HR 0.65, 95%CI [0.52, 0.80], p < 0.001), but higher in-hospital mortality (OR 2.04, 95%CI [1.04, 4.01], p = 0.039). CONCLUSION: In this cohort, relevant CAD was not associated with worse outcomes and should therefore not be considered a contraindication for LuTx. Nonetheless, cardiovascular events in CAD patients highlight the necessity of control of cardiovascular risk factors and a structured cardiac follow-up.

Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy.

BACKGROUND: Monoclonal antibodies (biologics) drastically changed severe asthma therapy. Mepolizumab (anti-interleukin (IL) 5), benralizumab (anti-IL5 receptor alpha), and dupilumab (anti-IL4/13) are the most used biologics in this context. While all biologics are efficient individually, the choice of biologic is complicated by insufficient data on their comparative long-term treatment efficacy. Here, we compare the real-life efficacy of these biologics in asthma therapy over 12 months. METHODS: 280 severe asthma patients treated with mepolizumab (129/280, 46%), benralizumab (83/280, 30%) or dupilumab (68/280, 24%) for one year were analyzed retrospectively. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels as well as responder status measured by the recently published "Biologic Asthma Response Score" (BARS). RESULTS: All biologics led to significant improvements in PF, ACT and OCS dose. Only Mepolizumab and Benralizumab significantly decreased the exacerbation rate, while only Mepolizumab and Dupilumab significantly decreased FeNO. Responder rates measured by BARS were high across all groups: roughly half of all patients achieved full response and most of the remainder achieved at least partial responder status. Overall, outcomes were similar between groups after both 6 and 12 months. CONCLUSIONS: All biologics showed great efficacy in individual parameters and high responder rates measured by BARS without a clinically relevant advantage for any antibody. Response was usually achieved after 6 months and retained at 12 months, emphasizing the utility of early response assessment.

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.

Initiation, response assessment, and switch of antibody therapies in patients with severe asthma - A survey among German specialists.

Background: For therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and switch. Objective: To assess current practice on all aspects of biologic therapy by specialists in Germany. Methods: A questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis. Results: Forty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between "responders", "partial responders" and "non-responders". Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP. Conclusion: This study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany.

Domestic Parasitic Infections in Patients with Asthma and Eosinophilia in Germany - Three Cases with Learnings in the Era of Anti- IL5 Treatments.

Eosinophilic inflammation is a hallmark of asthma, and blood eosinophilia has been established as a biomarker for phenotyping asthma and predicting the response to anti-IL5 treatments. Although parasitic infections are rare in European adults, they remain an important differential diagnosis for blood eosinophilia. We present three patients with both domestic parasitic infections and asthma to raise awareness of the potential challenge of eosinophilia and to provide experience in the management of parasitic infections in the setting of planned or ongoing anti-IL5 treatment. One, a patient from Croatia with moderate asthma but severe blood eosinophilia had an underlying Strongyloides stercoralis infection, with positive stool cultures. Second, a patient with severe allergic asthma and gastrointestinal symptoms had a positive S. stercoralis titer in serology with a clinical response to treatment with ivermectin. Third, a patient with severe nonallergic eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA) showed an increasing hepatic tumour under anti-IL5-receptor therapy. Positive serology confirmed the diagnosis of Echinococcus multilocularis, and albendazole therapy was initiated. Anti-IL5 therapies were safely started (Patient 2) or resumed (Patient 3) after the initiation of antiparasitic treatment. Screening for parasitic infections is useful in cases of hypereosinophilia, extrapulmonary symptoms or stay in endemic regions.

Biologics for severe asthma and beyond.

Advances in pathophysiological understanding and the elucidation of a type 2 inflammatory signature with interleukins 4, 5 and 13 at its center have led to the development of targeted antibody therapies that are now approved for the treatment of severe asthma. In suitable patients, these medications reduce asthma exacerbations and the necessity for oral corticosteroids, improve asthma control, quality of life and lung function. A proportion of patients with severe asthma may even achieve remission under ongoing biologic therapy. Type-2 inflammatory comorbidities are frequent in patients with severe asthma, sharing overlapping pathophysiology and may similarly respond to biologic treatment. Here, we give an overview of the six biologic therapies currently approved for severe asthma and review randomized clinical trials and real-life studies in asthma and other type-2 inflammatory diseases. We also discuss selection of biologics according to licensing criteria, asthma phenotype and biomarkers, monitoring of treatment response and proceedings in case of insufficient outcome under therapy.

Health Care Situation in the Treatment of Uncontrolled GINA Step 4/5 Patients in Germany.

Purpose: It has been estimated that, in 2019, 54,000 patients in Germany had uncontrolled GINA step 4/5 asthma. In the current study we analyzed which health care providers were involved in the management of these patients and their role in disease phenotyping. Patients and Methods: The year 2019 was retrospectively analyzed using the IQVIATM LRx, a longitudinal anonymized prescription database, and the electronic, anonymized medical records database, the IQVIA Disease Analyzer. Results: Of 54,000 uncontrolled GINA step 4/5 asthma patients in Germany, 52% had consulted both general practitioners (GPs) and pulmonologists, and 48% were seen exclusively by a GP. Of these 54,000 patients, 45% were being prescribed and were thus overusing short-acting ß2-agonists (SABAs) and oral corticosteroids (OCS) for ≥2 years, 26% for ≥3 years, and 16% for ≥4 years. In most regions, pulmonologists saw one of their uncontrolled GINA step 4/5 asthma patients per week. Laboratory tests from consultations with a GP were available for only 10% of patients referred to a pulmonologist. In 50% of uncontrolled asthma patients treated according to GINA step 4/5, these were initiated by the pulmonologist, and 34% received laboratory testing within the first year (in GINA step 4/5 asthma, the numbers are 20% and 18%, respectively). Conclusion: Fifty percent of uncontrolled asthma patients treated according to GINA step 4/5 were regularly seen by pulmonologists, who performed most of the phenotyping confirming their importance in the management of severe, uncontrolled asthma in Germany. To understand treatment pathways for these patients, further studies are needed.

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.

Characterization of Obesity in Severe Asthma in the German Asthma Net.

BACKGROUND: Asthma is increasingly recognized as heterogeneous, characterized by different endotypes, with obesity not only a distinct phenotype but a risk factor for severe asthma. OBJECTIVE: We sought to understand the associations of obesity with relevant parameters of severe asthma, including asthma control, disease burden, and lung function. METHODS: The German Asthma Net registry is a multicenter international real-life registry capturing long-term follow-up data. This analysis included 2213 patients (52 ± 16 years, 58% female, 29% with obesity [body mass index ≥30 kg/m2], 4.2 ± 4.3 exacerbations/year). The primary analysis assessed relationships between BMI and variables through univariate tests, followed by a multiple regression model. Secondary outcomes regarded clinically relevant variables in relation to weight groups. RESULTS: Patients with obesity were more frequently female, more likely to have depression and gastroesophageal reflux, and suffered from worse asthma control, lower quality of life, reduced static lung volumes, more pronounced hypoxemia, and higher blood neutrophil counts, all statistically significant. Blood eosinophils, exhaled nitric oxide, and total IgE were independent of obesity. In the multiple regression analysis, obesity was significantly associated with more frequent reflux and depression, reduced static lung function values, older age, poor asthma control, and long-acting muscarinic antagonist therapy, and inversely associated with bronchiectasis and nonsmoking status. CONCLUSION: In this large, well-characterized cohort, we identified the association of obesity with a significantly higher disease burden and a similar portfolio of inflammation type 2 markers in patients with and without obesity; therefore, patients with obesity seem similarly eligible for the treatment with biologics targeting these disease endotypes.

Clinical Impact of Physical Activity and Cough on Disease Progression in Fibrotic Interstitial Lung Disease.

Physical activity limitations and cough are common in patients with interstitial lung disease (ILD), potentially leading to reduced health-related quality of life. We aimed to compare physical activity and cough between patients with subjective, progressive idiopathic pulmonary fibrosis (IPF) and fibrotic non-IPF ILD. In this prospective observational study, wrist accelerometers were worn for seven consecutive days to track steps per day (SPD). Cough was evaluated using a visual analog scale (VAScough) at baseline and weekly for six months. We included 35 patients (IPF: n = 13; non-IPF: n = 22; mean ± SD age 61.8 ± 10.8 years; FVC 65.3 ± 21.7% predicted). Baseline mean ± SD SPD was 5008 ± 4234, with no differences between IPF and non-IPF ILD. At baseline, cough was reported by 94.3% patients (mean ± SD VAScough 3.3 ± 2.6). Compared to non-IPF ILD, patients with IPF had significantly higher burden of cough (p = 0.020), and experienced a greater increase in cough over six months (p = 0.009). Patients who died or underwent lung transplantation (n = 5), had significantly lower SPD (p = 0.007) and higher VAScough (p = 0.047). Long-term follow up identified VAScough (HR: 1.387; 95%-CI 1.081-1.781; p = 0.010) and SPD (per 1000 SPD: HR 0.606; 95%-CI: 0.412-0.892; p = 0.011) as significant predictors for transplant-free survival. In conclusion, although activity didn't differ between IPF and non-IPF ILD, cough burden was significantly greater in IPF. SPD and VAScough differed significantly in patients who subsequently experienced disease progression and were associated with long-term transplant-free survival, calling for better acknowledgement of both parameters in disease management.

Response to Biologics and Clinical Remission in the Adult German Asthma Net Severe Asthma Registry Cohort.

BACKGROUND: Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in severe asthma. OBJECTIVE: To analyze the response and remission in the German Asthma Net severe asthma registry cohort. METHODS: We included adults not using a biologic at baseline (V0) and compared patients treated between V0 and 1-year visit (V1) without using a biologic (group A) to patients starting with a biologic after V0 and continuing it up to V1 (group B). We applied the Biologics Asthma Response Score to quantify composite response in good, intermediate, or insufficient. We defined clinical remission (R) as absence of significant symptoms (Asthma Control Test score ≥ 20 at V1) in the absence of exacerbations and oral corticosteroid therapy. RESULTS: Group A included 233 and group B 210 patients, the latter receiving omalizumab (n = 33), mepolizumab (n = 40), benralizumab (n = 81), reslizumab (n = 1), or dupilumab (n = 56). At baseline, group B had less often an allergic phenotype (35.2% vs 41.6%), lower Asthma Control Test score (median, 12 vs 14), more exacerbations in the past year (median, 3 vs 2), and more often high-dose inhaled corticosteroid treatment (71.4% vs 51.5%) than group A. After 1 year of treatment, rates of response (good: 61.4% vs 34.8%; intermediate: 26.7% vs 42.9%; insufficient: 11.9% vs. 22.3%) and/or clinical remission (37.6% vs 17.2%) were higher in group B than in group A. CONCLUSIONS: Despite more severe asthma at baseline, patients treated with biologics had a markedly higher probability of achieving good clinical response and/or remission than patients treated without biologics.

Case report: Central venous catheter thrombosis complicated by chronic thromboembolic disease/pulmonary hypertension in two children requiring parenteral nutrition.

Chronic thromboembolic pulmonary hypertension is a rare but life-threatening complication of long-term central venous catheters (CVC) in children. However, evidence in terms of potential treatment strategies and outcome data remains scarce. We describe two cases of CVC-related thrombosis (Hickman-catheter) complicated by recurrent pulmonary emboli. One patient experienced a complete thromboembolic obstruction of the right pulmonary artery with normal pulmonary pressures and the second patient suffered from a central thromboembolic obstruction of both pulmonary arteries associated with severe pulmonary hypertension. Both patients successfully underwent surgical thromboendarterectomy with deep hypothermic circulatory arrest.

Antiviral CD8+ T-cell immune responses are impaired by cigarette smoke and in COPD.

BACKGROUND: Virus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8+ T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells. METHODS: We analysed the effects of cigarette smoke on cytokine- and virus-mediated induction of the immunoproteasome in vitro, ex vivo and in vivo using RNA and Western blot analyses. CD8+ T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8+ T-cell numbers were determined in patients' peripheral blood using tetramer technology. RESULTS: Cigarette smoke impaired the induction of the immunoproteasome by cytokine signalling and viral infection in lung cells in vitro, ex vivo and in vivo. In addition, cigarette smoke altered the peptide repertoire of antigens presented on MHC class I molecules under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8+ T-cells was dampened by cigarette smoke. COPD patients exhibited reduced numbers of circulating IAV-specific CD8+ T-cells compared to healthy controls and asthmatics. CONCLUSION: Our data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8+ T-cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections.

Real-World Experience on the Use of Mepolizumab from the Severe Asthma Registry of the German Asthma Net (MepoGAN-Study).

Purpose: The German Asthma Net (GAN) operates a Severe Asthma Registry that provides an overview of the clinical presentation and management of patients with severe asthma. Based upon data from the GAN registry, the MepoGAN study aimed to describe clinical profiles and treatment outcomes of patients who were treated with the anti-IL-5 monoclonal antibody mepolizumab (NucalaTM) in routine practice in Germany. Patients and Methods: The MepoGAN study is a descriptive retrospective non-interventional cohort study. Mepolizumab patients enrolled in the GAN registry were evaluated with results being described in two different data sets: Cohort 1 (n=131) started on mepolizumab when the patients entered the registry. Results were reported after 4 months of therapy. Patients in Cohort 2 (n=220) were on treatment with mepolizumab at the time of enrollment and follow-up data were collected after a further year of treatment. Outcome measures included asthma control, lung function, disease symptoms, OCS use, and exacerbations. Results: Patients enrolled in the registry who started on mepolizumab in Cohort 1 had a mean age of 55 years, were former smokers in 51% of the cases, had a mean blood eosinophil count of 500 cells/µL, and frequently had maintenance OCS use (55%). In this real-world setting, mepolizumab therapy was associated with a clinically relevant reduction in blood eosinophils (-445.7 cells/µL), OCS use (-30%), and improvement in asthma control. Fifty-five percent (vs 10% at baseline) of the patients reported controlled or partially controlled asthma 4 months after starting therapy. In patients who were already treated with mepolizumab at registry enrollment (Cohort 2), asthma control and lung function remained stable after a further year of observation. Conclusion: The GAN registry data confirm the effectiveness of mepolizumab in a real-world setting. Treatment benefits are maintained over time. While the asthma of patients treated in routine practice was more severe, the results observed with mepolizumab are broadly consistent with RCTs.

[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.

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis.

BACKGROUND: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. METHODS: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. RESULTS: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. CONCLUSIONS: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities.

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.