Background: Benralizumab reduces exacerbations and long-term oral glucocorticosteroid (OCS) exposure in patients with severe eosinophilic asthma. In patients with eosinophilic granulomatosis with polyangiitis (EGPA), uncontrolled symptoms and exacerbations of asthma and chronic rhinosinusitis (CRS) are important reasons for continued OCS therapies. We aimed to describe outcomes of patients with severe asthma and EGPA treated with benralizumab in real-life. Methods: We retrospectively analyzed adult patients from the Severe Asthma Unit at LMU Munich diagnosed with severe asthma and EGPA treated with benralizumab, differentiating two groups: Group A, patients with a stable daily OCS dose and diagnosis of EGPA > 6 months ago; and Group B, patients treated with high-dose daily OCS due to recent diagnosis of EGPA < 6 months ago. We compared outcome parameters at baseline and 12 months after initiation of benralizumab, including respiratory exacerbations, daily OCS dose, and lung function. Results: Group A included 17 patients, all receiving OCS therapy and additional immunosuppressants; 15 patients (88%) continued benralizumab for more than 12 months, demonstrating a significant reduction in daily OCS dose and exacerbations while FEV1 increased. Group B included 9 patients, all with high-dose daily OCS and some receiving cyclophosphamide pulse therapy for life-threatening disease. Benralizumab addition during induction was well tolerated. A total of 7/9 (78%) continued benralizumab for more than 12 months and preserved EGPA remission at the 12-month timepoint. Conclusion: In this real-life cohort of patients with severe asthma and EGPA, benralizumab initiation during remission maintenance reduced respiratory exacerbations and daily OCS dose. Benralizumab initiation during remission induction was associated with a high rate of clinical EGPA remission.

Background: Pulmonary hypertension (PH) associated with COPD contributes to morbidity and mortality. Further characterisation to improve management is warranted. The aim of the study was to apply the recently proposed PH classification and to assess the association of lung volume involvement and PH over the course of disease in patients with advanced COPD. Methods: Patients with COPD undergoing transplant evaluation, including right heart catheterisation were included irrespective of the likelihood of having PH. Spirometry, plethysmography and computed tomography were used to assess the degree of parenchymal and vascular involvement. Follow-up investigation was performed for 18±12 months. The 2022 European Society of Cardiology/European Respiratory Society guidelines were used for classification of PH. Results: In total, 340 patients were included and 639 right heart catheters were assessed. The majority of patients were classified as no PH (n=131, 38%) or nonsevere PH (n=133, 39%), whereas severe COPD-PH was present in 26 patients (8%). Patients with severe COPD-PH had similar degrees of airflow obstruction but lower lung volumes. Further, pulmonary vascular resistance (PVR) correlated negatively with residual volume. Interstitial lung abnormalities were present in 11 patients (3%) and scattered across all PH groups. Follow-up (n=141, 41.5%) demonstrated a low rate of deterioration to severe COPD-PH (4%). However, an increase of PVR was common and was associated with a decrease of total lung capacity. Conclusion: Unbiased longitudinal invasive follow-up and assessment of lung volumes by plethysmography provided evidence of an association of lung volume and PVR.

Dupilumab is an IL-4Rα antibody approved for treatment of severe asthma. Real-world data on the continuation and cessation patterns of dupilumab and long-term treatment efficacy are scarce. We sought to analyze real-world, long-term treatment outcomes and to evaluate trajectories of patients continuing or discontinuing dupilumab therapy over a 3-year period. This multicenter, retrospective, real-world cohort study included patients with severe asthma who started dupilumab before March 2021. Data on asthma control, medication, lung function, and annualized exacerbation rates were collected at baseline and 3, 12, and 36 months after initiation of dupilumab therapy. Asthma remission was assessed at 12 months and 36 months after dupilumab initiation. Of 160 included patients, 95 patients (59%) continued dupilumab therapy for 36 months; 65 patients (41%) discontinued therapy after a median time of therapy of 8 months. Patients who continued dupilumab for 36 months had significant reductions in annual exacerbations (-1; P < .0001) and oral corticosteroid dose (-5.5 mg/day; P < .001) as well as significant improvements in asthma control (asthma control test +5; P < .0001) and lung function (percent predicted of FEV₁ +7%; P < .001) compared with baseline. Of patients who continued dupilumab, 30% achieved remission at 12 months, and 26% achieved remission at 36 months. Of the 65 patients who discontinued therapy, 55 switched to another antibody, and 10 did not receive further antibody treatment. Dupilumab represents an effective long-term treatment option for patients with severe asthma, with sustained treatment effects up to 36 months. Importantly, a relevant proportion of patients achieved remission in this pretreated population.

Background: Pleural effusions of unknown etiology have been demonstrated to be associated with poor prognosis in lung allograft recipients. We aimed to identify novel risk factors for pleural effusions after lung transplantation (LTX) and to shed light on their association with allograft function and survival, differentiating early and late pleural effusions after LTX. Methods: We performed a retrospective study of all LTX recipients transplanted at the LMU Klinikum Munich from 2013 to 2018. We recorded all pleural effusions requiring thoracocentesis and analyzed the corresponding clinical data. A total of 426 pleural effusions in 369 lung allograft recipients with a median follow‐up time of 6.9 years were analyzed. Results: Both early (90 days after LTX) were associated with increased mortality, with a strong mortality risk for late pleural effusions (HR 4.0). Increased mortality in patients with early pleural effusions might be mediated by a higher risk for baseline lung allograft dysfunction (BLAD). Early pleural effusions were associated with underlying obstructive disease, relative donor organ undersizing and clamshell thoracotomy. Notably, (partial) resection of the parietal pleura during LTX was not associated with pleural effusions. Conclusions: This study underlines the importance of pleural effusions after LTX. All pleural effusions were associated with increased mortality, while only early pleural effusions were associated with BLAD. The mechanisms linking pleural effusions to BLAD and to higher mortality remain unknown and will be investigated in future, prospective cohorts.

Background: Baseline lung allograft dysfunction (BLAD) is characterised by the failure to achieve normal baseline lung function after lung transplantation (LTX), affecting over a third of LTX recipients and conveying significant mortality. While previous studies identified BLAD as a risk factor for mortality, evolution, transitions and risk factors influencing transitions from BLAD to normal lung function or death/retransplantation remain unknown. Methods: We conducted a retrospective study of 472 LTX recipients transplanted between 2010 and 2018, using a Markov multistate model to characterise lung function evolution. The model investigated transitions between “indeterminate”, “BLAD”, “normal baseline lung function” and “death/retransplantation” states. We modelled state transitions, association of BLAD with mortality, and risk factors influencing transitions and mortality through respective states. Results: Our study confirms a higher mortality risk for BLAD, particularly in single LTX (SLTX) compared to double LTX (DLTX) recipients. DLTX recipients with obstructive underlying disease were more likely to recover from BLAD (hazard ratio (HR) 3.1) but faced higher mortality if remaining in BLAD (HR 2.6). Chronic lung allograft dysfunction had a strong association with mortality in patients with normal baseline lung function (HR 5.1) but also to a lesser extent in BLAD patients (HR 1.8). Longitudinal analysis demonstrated that DLTX recipients often recover from BLAD, while SLTX recipients rarely achieve normal lung function if starting in BLAD. Conclusions: Our study highlights differences in lung function evolution between SLTX and DLTX recipients and investigates for the first time prevalence and risk factors for transitions between BLAD and non-BLAD states, as well as risk factors influencing BLAD-related mortality in LTX recipients.