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Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease, which is usually type 2-mediated in the western hemisphere, associated with severe therapeutic and socioeconomic challenges. The first targeted systemic treatment option for severe uncontrolled CRSwNP is a human monoclonal antibody against the interleukin-4 receptor α (IL-4Rα) subunit called dupilumab, which was approved for subcutaneous administration in Germany in October 2019. The purpose of this study is to investigate the efficacy of dupilumab in real life in patients treated with dupilumab in label according to license in our department in 2019–2021. Materials and methods Since October 2019, we have investigated 40 patients (18 men, 22 women) treated with dupilumab in a single-center, retrospective single-arm longitudinal study. The following parameters were collected before treatment (baseline), at 1 month, 4 months, 7 months, 10 months, and 13 months: the Sino-Nasal Outcome Test-22 (SNOT-22), the forced expiratory pressure in 1 s (FEV-1), the olfactometry using Sniffin' Sticks-12 identification test (SSIT), a visual analog scale of the total complaints, the Nasal Polyp Score (NPS), histologic findings as well as total serum IgE, eosinophilic cationic protein in serum and blood eosinophils. Results The average age was 52.7 years (± 15.3). The follow-up period was 13 months. The SNOT-22 average was 60 points (± 22.2) at the first visit, 28.2 points (± 17.1) after 4 months and 20.8 points (± 17.7) after 13 months. The NPS was 4.3 points (± 1.5), after 4 months 2.1 points (± 1.3) and after 13 months 1.4 points (± 1.1). Olfactometry showed 3.2 points (± 3.7) at the baseline, 7.0 points (± 4.0) after 4 months and 7.8 points (± 3.5) after 13 months. The other parameters also improved. Most parameters showed linear dependence in the slopes under therapy (p Conclusion There is a clear improvement in the medical condition and symptoms in all categories mentioned under therapy with dupilumab, as well as a reduction in the need for systemic glucocorticoids and revision surgery as rescue treatment. Our results show that dupilumab tends to be an effective therapy alternative for severe CRSwNP.

ZusammenfassungOrganbezogene Folgeerscheinungen nach COVID-19 sind häufig und vielgestaltig. Ab 4 Wochen nach Akutinfektion mit SARS-CoV‑2 werden sie unter dem Begriff „Long-COVID“ zusammengefasst.Nach schweren Akutverläufen treten organbezogene Folgeerscheinungen häufiger auf. Dauer und Intensität variieren jedoch interindividuell stark. Die SARS-CoV-2-Spezifität der Folgeerscheinungen ist ebenfalls weiter unklar. Während sich in der Frühphase nach schweren Verläufen zumeist pulmonale Folgeerscheinungen einstellen, müssen diese nicht auf die Lunge begrenzt bleiben, sondern können prinzipiell jedes Organ betreffen. Die adäquate Diagnostik von COVID-19-Folgeerscheinungen stellt daher eine interdisziplinäre Herausforderung dar. Auch die Therapie richtet sich nach Art, Umfang und Ursache der jeweiligen Folgeerscheinung. Allgemeinmedikamentöse oder zielgerichtete Therapieoptionen gegen Long-COVID bestehen bisher nicht.Im vorliegenden Übersichtsartikel berichten wir über Häufigkeit, Dauer, Spezifität sowie Art und Umfang organspezifischer COVID-19-Folgeerscheinungen und geben einen Überblick über diagnostisches und therapeutisches Vorgehen (mit Datenstand November 2021).

γ-glutamyl transferase (GGT), the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers in several cardiovascular diseases, but their relevance in pulmonary hypertension (PH) is not fully understood. We aimed to assess their prognostic value in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).We retrospectively analyzed 731 incident patients with idiopathic PAH or CTEPH who entered the Giessen PH registry during 1993-2019. A risk stratification score based on GGT, AST/ALT ratio, and NLR tertiles was compared with a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) risk stratification scheme. Associations with survival were evaluated using Kaplan-Meier and Cox regression analyses. External validation was performed in 311 patients with various types of PAH or CTEPH from a second German center.GGT levels, AST/ALT, and NLR independently predicted mortality at baseline and during follow-up. The scoring system based on these biomarkers predicted mortality at baseline and during follow-up (both log-rank p0.001; hazard ratio [95% confidence interval], high vs low risk: baseline, 7.6 [3.9, 15.0]; follow-up, 13.3 [4.8, 37.1]). Five-year survival of low, intermediate, and high risk groups was 92%, 76%, and 51%, respectively, at baseline and 95%, 78%, and 50%, respectively, during follow-up. Our scoring system showed characteristics comparable to the ESC/ERS scheme, and predicted mortality in the validation cohort.GGT, AST/ALT, and NLR were reliable prognostic biomarkers at baseline and during follow-up, with predictive power comparable to the gold standard for risk stratification.

Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as a model for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were published during the last 2 years. Additionally, there were more new publications, which were considered for this review article. In this context, this review article provides a current update and overview of sarcoidosis. Pathophysiologically, there is an increasing understanding of the complex processes and interactions involved in the inflammatory processes and granuloma formation. The probability of a diagnosis of sarcoidosis is determined by compatible histology, the exclusion of differential diagnoses and if possible evidence of a multiorgan manifestation. The clinical course is variable and ranges from an asymptomatic manifestation to severe life-threatening organ failure. The most frequently affected organ are the lungs. Pulmonary fibrosis is the most severe form and is also decisive for mortality. An increasing focus is on the extrapulmonary organ manifestations, in particular, cardiac, hepatosplenic, gastrointestinal, renal, ocular and neurological involvement. Treatment, which consists primarily of immunosuppression, should be initiated in cases of organ-threatening or quality of life-impairing activity of the disease. Additional organ-specific management must also be evaluated. In cases of organ failure transplantation should be considered. Due to the limited evidence especially for the treatment of multiorgan sarcoidosis, when possible, patients with this disease should be included in clinical trials.Die Sarkoidose ist die häufigste immunologisch bedingte Granulomatose und kann beispielhaft für das Verständnis von Erkrankungen aus diesem Formenkreis herangezogen werden. Die Evidenz zur Diagnostik und Therapie ist bisher limitiert. Umso bedeutender ist es, dass in den letzten 2 Jahren gleich 2 neue Leitlinien zur Diagnose und Therapie veröffentlicht wurden. Darüber hinaus gab es weitere neue Publikationen, die in diesem Beitrag berücksichtigt werden. In diesem Kontext soll die vorliegende Übersichtsarbeit einen aktuellen Überblick über die Sarkoidose liefern. Pathophysiologisch zeigt sich ein zunehmendes Verständnis der komplexen Prozesse und Interaktionen, die an der Inflammation und Granulombildung beteiligt sind. Die Wahrscheinlichkeit einer Sarkoidosediagnose ist durch die Gewinnung einer passenden Histologie, den Ausschluss von Differenzialdiagnosen und möglichst den Nachweis einer Multiorganmanifestation bestimmt. Der klinische Verlauf ist variabel und reicht von einer asymptomatischen Manifestation bis zum schweren lebensbedrohlichen Organversagen. Das am häufigsten betroffene Organ ist die Lunge. Die schwerste Form ist dabei die Lungenfibrose, die auch mortalitätsbestimmend ist. Ein zunehmender Fokus liegt auf den extrapulmonalen Organmanifestationen, insbesondere der kardialen, hepatosplenischen, gastrointestinalen, renalen, okulären und neurologischen Beteiligung. Die Therapie sollte bei organbedrohender oder lebensqualitätseinschränkender Aktivität eingeleitet werden und ist geprägt durch eine Immunsuppression. Weitere organspezifische Therapien sind ebenfalls zu evaluieren. Bei einem Organversagen kann eine Transplantation erwogen werden. Aufgrund der eingeschränkten Datenlage, insbesondere in der Therapie der Multiorgansarkoidose, sollten Patienten mit dieser Erkrankung möglichst in Studien eingeschlossen werden.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease, which is usually type 2-mediated in the western hemisphere, associated with severe therapeutic and socioeconomic challenges. The first targeted systemic treatment option for severe uncontrolled CRSwNP is a human monoclonal antibody against the interleukin-4 receptor α (IL-4Rα) subunit called dupilumab, which was approved for subcutaneous administration in Germany in October 2019. The purpose of this study is to investigate the efficacy of dupilumab in real life in patients treated with dupilumab in label according to license in our department in 2019-2021.Since October 2019, we have investigated 40 patients (18 men, 22 women) treated with dupilumab in a single-center, retrospective single-arm longitudinal study. The following parameters were collected before treatment (baseline), at 1 month, 4 months, 7 months, 10 months, and 13 months: the Sino-Nasal Outcome Test-22 (SNOT-22), the forced expiratory pressure in 1 s (FEV-1), the olfactometry using Sniffin' Sticks-12 identification test (SSIT), a visual analog scale of the total complaints, the Nasal Polyp Score (NPS), histologic findings as well as total serum IgE, eosinophilic cationic protein in serum and blood eosinophils.The average age was 52.7 years (± 15.3). The follow-up period was 13 months. The SNOT-22 average was 60 points (± 22.2) at the first visit, 28.2 points (± 17.1) after 4 months and 20.8 points (± 17.7) after 13 months. The NPS was 4.3 points (± 1.5), after 4 months 2.1 points (± 1.3) and after 13 months 1.4 points (± 1.1). Olfactometry showed 3.2 points (± 3.7) at the baseline, 7.0 points (± 4.0) after 4 months and 7.8 points (± 3.5) after 13 months. The other parameters also improved. Most parameters showed linear dependence in the slopes under therapy (p 0.001). Adverse side effects were mostly only mild, and no rescue therapy was needed.There is a clear improvement in the medical condition and symptoms in all categories mentioned under therapy with dupilumab, as well as a reduction in the need for systemic glucocorticoids and revision surgery as rescue treatment. Our results show that dupilumab tends to be an effective therapy alternative for severe CRSwNP.

While several studies have described the clinical course of patients with coronavirus disease 2019 (COVID-19), direct comparisons with patients with seasonal influenza are scarce. We compared 166 patients with COVID-19 diagnosed between February 27 and June 14, 2020, and 255 patients with seasonal influenza diagnosed during the 2017–18 season at the same hospital to describe common features and differences in clinical characteristics and course of disease. Patients with COVID-19 were younger (median age [IQR], 59 [45–71] vs 66 [52–77]; P

Purpose Symptoms often persistent for more than 4 weeks after COVID-19—now commonly referred to as ‘Long COVID’. Independent of initial disease severity or pathological pulmonary functions tests, fatigue, exertional intolerance and dyspnea are among the most common COVID-19 sequelae. We hypothesized that respiratory muscle dysfunction might be prevalent in persistently symptomatic patients after COVID-19 with self-reported exercise intolerance. Methods In a small cross-sectional pilot study (n = 67) of mild-to-moderate (nonhospitalized) and moderate-to-critical convalescent (formerly hospitalized) patients presenting to our outpatient clinic approx. 5 months after acute infection, we measured neuroventilatory activity P0.1, inspiratory muscle strength (PImax) and total respiratory muscle strain (P0.1/PImax) in addition to standard pulmonary functions tests, capillary blood gas analysis, 6 min walking tests and functional questionnaires. Results Pathological P0.1/PImax was found in 88% of symptomatic patients. Mean PImax was reduced in hospitalized patients, but reduced PImax was also found in 65% of nonhospitalized patients. Mean P0.1 was pathologically increased in both groups. Increased P0.1 was associated with exercise-induced deoxygenation, impaired exercise tolerance, decreased activity and productivity and worse Post-COVID-19 functional status scale. Pathological changes in P0.1, PImax or P0.1/PImax were not associated with pre-existing conditions. Conclusions Our findings point towards respiratory muscle dysfunction as a novel aspect of COVID-19 sequelae. Thus, we strongly advocate for systematic respiratory muscle testing during the diagnostic workup of persistently symptomatic, convalescent COVID-19 patients.

Organ-specific sequelae after COVID-19 occur frequently and are highly diverse in their features. Sequelae and symptoms persisting for more than four weeks after COVID-19 define the condition "long COVID."Organ-specific sequelae of COVID-19 generally occur more often after severe disease. Yet, duration and intensity of organ-specific sequelae are highly variable. While pulmonary sequelae typically persist after more severe acute disease, COVID-19 sequelae may also develop weeks after infection and can affect any organ. The degree of SARS-CoV‑2 specificity of COVID-19 sequelae, however, remains unclear. Thus, diagnosis and treatment of COVID-19 sequelae represent an interdisciplinary challenge. Diagnostic and therapeutic approaches are guided by type, extent, and cause of the specific sequelae as targeted therapy options for long COVID are lacking.In the present work, we review current knowledge regarding the prevalence/incidence, duration, specificity, type, and extent of organ-specific COVID-19 sequelae and summarize current diagnostic and therapeutic strategies (as of November 2021).Organbezogene Folgeerscheinungen nach COVID-19 sind häufig und vielgestaltig. Ab 4 Wochen nach Akutinfektion mit SARS-CoV‑2 werden sie unter dem Begriff „Long-COVID“ zusammengefasst.Nach schweren Akutverläufen treten organbezogene Folgeerscheinungen häufiger auf. Dauer und Intensität variieren jedoch interindividuell stark. Die SARS-CoV-2-Spezifität der Folgeerscheinungen ist ebenfalls weiter unklar. Während sich in der Frühphase nach schweren Verläufen zumeist pulmonale Folgeerscheinungen einstellen, müssen diese nicht auf die Lunge begrenzt bleiben, sondern können prinzipiell jedes Organ betreffen. Die adäquate Diagnostik von COVID-19-Folgeerscheinungen stellt daher eine interdisziplinäre Herausforderung dar. Auch die Therapie richtet sich nach Art, Umfang und Ursache der jeweiligen Folgeerscheinung. Allgemeinmedikamentöse oder zielgerichtete Therapieoptionen gegen Long-COVID bestehen bisher nicht.Im vorliegenden Übersichtsartikel berichten wir über Häufigkeit, Dauer, Spezifität sowie Art und Umfang organspezifischer COVID-19-Folgeerscheinungen und geben einen Überblick über diagnostisches und therapeutisches Vorgehen (mit Datenstand November 2021).

In a cross-sectional analysis, we have identified a high prevalence of respiratory muscle dysfunction in persistently symptomatic patients after COVID-19 (‘Long COVID’). Respiratory muscle impairment in these patients was associated with exercise-induced deoxygenation, impaired exercise tolerance, activity and functional outcomes after COVID-19.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

Aim: We aimed to develop a candidate-based integrative public data mining strategy for validation of novel prognostic markers in lung adenocarcinoma. Materials & methods: An in silico approach integrating meta-analyses of publicly available clinical information linked RNA expression, gene copy number and mutation datasets combined with independent immunohistochemistry and survival datasets. Results: After validation of pipeline integrity utilizing data from the well-characterized prognostic factor Ki-67, prognostic impact of the calcium- and integrin-binding protein, CIB1, was analyzed. CIB1 was overexpressed in lung adenocarcinoma which correlated with pathological tumor and pathological lymph node status and impaired overall/progression-free survival. In multivariate analyses, CIB1 emerged as UICC stage-independent risk factor for impaired survival. Conclusion: Our pipeline holds promise to facilitate further identification and validation of novel lung cancer-associated prognostic markers.

Key message Granulomatosis with polyangiitis (GPA) is a potentially life‐threatening disease that affects all ages. As the disease may be rapidly progressive, the undelayed recognition of its inflammatory activity is critical. This is especially important in central airway involvement, which contributes to morbidity and mortality., We present the case of a 17‐year‐old boy with granulomatosis with polyangiitis (GPA) with central airway involvement.

Background Low partial pressure of blood carbon dioxide (PaCO2) is common in patients with pulmonary arterial hypertension (PAH) and may inform on clinical outcomes. We investigated whether PaCO2 measurements could provide prognostic information in addition to standard risk assessment in this group of patients. Methods We conducted a retrospective observational cohort study on patients with newly diagnosed idiopathic, heritable or drug/toxin-induced PAH recruited from two European centres. Arterialised capillary blood gas analyses at diagnosis and follow-up were incorporated into standard risk assessment strategies and related to outcomes, defined as lung transplant or death. C statistics from receiver-operated characteristics and Cox regression models were used to assess the predictive value of models with and without PaCO2 measurements. Unsupervised clustering was applied to assess the relation of PaCO2 to haemodynamic and pulmonary function variables. Results Low PaCO2 measured at diagnosis and follow-up was significantly associated with inferior outcomes in 204 patients with PAH. PaCO2 provided prognostic information independent of established non-invasive variables. Integrating PaCO2 in risk strata improved C statistics of non-invasive and mixed invasive/non-invasive models, and revealed more accurate outcome estimates in regression models. Pairwise correlation and unsupervised cluster analyses supported a link between PaCO2 and haemodynamic variables, particularly with cardiac output, in PAH. Conclusions Measuring PaCO2 at diagnosis and during follow-up in patients with PAH provided independent prognostic information and has the potential to improve current risk assessment strategies.

Objectives To compare magnetic resonance imaging (MRI)-based and laryngoscopy-based subglottic stenosis (SGS) grading with pulmonary function tests (PFT) in patients with granulomatosis with polyangiitis (GPA). Methods In this retrospective study we included 118 examinations of 44 patients with GPA and suspected SGS. All patients underwent MRI, laryngoscopy, and PFT. Stenosis was graded on a 4-point scale by endoscopy and MRI using the Meyer-Cotton (MC)-Score (score1: ≤50%; 2: 51-70%; 3: 71-99%; 4: 100%) and as percentage by MRI. Results were compared with peak expiratory flow (PEF) and maximum inspiratory flow (MIF) from PFT, serving as objective functional reference. Results In MRI, 112/118 examinations (95%) were rated positive for SGS (n=82: grade1; n=26: grade2; n=4: grade3) whereas in laryngoscopy 105/118 examinations (89%) were rated positive for SGS (n=73: grade1; n=24: grade2; n=8: grade3). MRI and laryngoscopy agreed in 75 of 118 examinations (64%). MRI determined higher scores in 20 (17%) and lower scores in 23 (19%) examinations compared to laryngoscopy. MC-scores as determined by both MRI and laryngoscopy showed comparable correlations with PEF (r=-0.363, p=0.016 and r=-0.376, p=0.012, respectively) and MIF (r=-0.340, p=0.024 and r=-0.320, p=0.034, respectively). Highest correlation was found between MRI-based stenosis grading in percentage with PEF (r=-0.441, p=0.003) and MIF (r=-0.413, p=0.005). Conclusions MRI and laryngoscopy provide comparable results for grading of SGS in GPA and correlate well with PFT. MRI is an attractive non-invasive and radiation free alternative for monitoring the severity of SGS in patients with GPA. This article is protected by copyright. All rights reserved.

Resumen Introduccion El tratamiento endoscopico de reduccion del volumen pulmonar mediante espirales (RVPE) es una opcion para determinados pacientes con enfisema grave. El estudio se llevo a cabo para determinar la incidencia de complicaciones hemorragicas tras el tratamiento de RVPE, identificar los factores de riesgo y debatir las opciones terapeuticas en los casos sin resolucion espontanea de la hemoptisis. Metodos Estudio observacional retrospectivo efectuado en el Departamento de Medicina Respiratoria del University Medical Center Hamburg-Eppendorf que incluyo a todos los pacientes sometidos a RVPE entre el 1 de abril del 2012 y el 30 de septiembre del 2015. Resultados Durante el periodo de estudio se practicaron 101 procedimientos de RVPE en 62 pacientes. Despues de la intervencion, se observo hemorragia temprana en un 65,3% de los casos. La probabilidad de presentar hemoptisis fue significativamente mayor en los pacientes que recibian acido acetilsalicilico (p = 0,005). La hemoptisis se resolvio espontaneamente en un 98,5% de los casos. En el caso de un paciente (1,5%) que presento hemoptisis persistente, se logro el cese de la hemorragia embolizando la arteria bronquial. La estancia hospitalaria fue significativamente mas prolongada en los pacientes que presentaron hemoptisis (p = 0,01). En cuanto a las exacerbaciones de la enfermedad pulmonar obstructiva cronica, en las 4 semanas siguientes al procedimiento de RVPE no se observaron diferencias significativas entre los pacientes con y sin hemoptisis (p = 0,18). Tres pacientes (3,0%) presentaron complicaciones hemorragicas tardias. Dos de estos se sometieron a embolizacion de la arteria bronquial que puso fin a la hemorragia de manera satisfactoria. Conclusiones La hemorragia de poco volumen y autolimitada es un hallazgo frecuente en los primeros dias despues del tratamiento de RVPE. Sin embargo, tanto en los dias siguientes a la intervencion de RVPE como mas adelante tambien puede aparecer una hemorragia persistente. En estos casos, la embolizacion de la arteria bronquial fue un abordaje viable y satisfactorio para lograr el cese del sangrado.

Introduction Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. This study was conducted to determine the incidence of bleeding complications after LVRC treatment, to identify risk factors and to discuss treatment options in cases of hemoptysis which does not resolve spontaneously. Methods Retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf in all subjects in whom LVRC treatment was performed between April 1, 2012 and September 30, 2015. Results During the study period, 101 LVRC procedures were performed in 62 subjects. Early post-procedural bleeding was encountered in 65.3% of cases. Hemoptysis was significantly more likely to occur in patients receiving acetylsalicylic acid (P=0.005). Hemoptysis resolved spontaneously in 98.5% of cases. In the one case (1.5%) with persistent hemoptysis, bronchial artery embolization was successful in terminating bleeding. Hospital stay was significantly prolonged in subjects with hemoptysis (P=0.01). No significant differences were found between subjects with or without hemoptysis in terms of chronic obstructive pulmonary disease exacerbations within four weeks after LVRC treatment (P=0.18). Late bleeding complications were observed in 3 subjects (3.0%). In 2 of these cases, bronchial artery embolization was performed successfully terminating the bleeding. Conclusions Self-limiting low volume bleeding is a common finding in the first days after LVRC treatment. However, persistent bleeding may occur in the early post-procedural phase and late after LVRC treatment. In these cases, bronchial artery embolization was a feasible and successful approach to terminating bleeding.

While antifibrotic therapy is approved for idiopathic pulmonary fibrosis (IPF) based on clinical trials, we aimed to assess the effects of such treatment under real life conditions. We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients in 20 ILD expert centers in Germany. Propensity scores were applied to account for known differences in baseline characteristics of patients with and without antifibrotic therapy. In 588 patients suitable for analysis, mean age was 69.8 ± 9.1 years, 81.0% were males. Mean duration of IPF since diagnosis was 1.8 ± 3.4 years. The mean % of predicted at baseline was 68.6 ± 18.8 for forced vital capacity (FVC) and 37.8 ± 35.4 for diffusion capacity (DLCO). During a mean follow-up of 1.2 ± 0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival was 92% vs. 78% and 76% vs. 63% for patients with vs. without antifibrotic therapy (Figure). The risk of death was 37% lower in patients with antifibrotic therapy (Hazard Ratio 0.63, 95%CI: 0.45-0.87; p=0.005). The result was robust (and remained statistically significant) on multivariable analysis. Patients on antifibrotic therapy did not statistically significantly differ in the decline of FVC and DLCO compared to patients without such treatment.

Background Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry. Methods Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George’s Respiratory Questionnaire (SGRQ) were used. Results Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DLCO% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DLCO % predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DLCO. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p

Background: Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. In the advanced stages, emphysema leads to respiratory failure: hypoxemia and eventually chronic hypercapnic respiratory failure. It can be hypothesized that LVRC treatment, a procedure targeting hyperinflation and thereby reducing ventilatory workload, may be especially beneficial in patients with chronic hypercapnic respiratory failure. This study was conducted to gain first insights into the effects and the safety of LVRC treatment in patients with emphysema and chronic hypercapnic respiratory failure. Methods: A retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf, Germany on all patients with chronic hypercapnic respiratory failure in whom bilateral LVRC treatment was performed between 1 April 2012 and 30 September 2015. Results: During the study period, bilateral LVRC treatment was performed in 10 patients with chronic hypercapnic respiratory failure. Compared with baseline, bilateral LVRC treatment led to a significant increase in mean forced expiratory volume in one second (FEV1) from 0.5 ± 0.1 l to 0.6 ± 0.2 l ( p = 0.004), a decrease in residual volume (RV) from 6.1 ± 0.9 l to 5.6 ± 1.1 l ( p = 0.02) and a reduction in partial pressure of carbon dioxide in arterial blood (PaCO2) from 53 ± 5 mmHg to 48 ± 4 mmHg ( p = 0.03). One case of hemoptysis requiring readmission to hospital was the only severe adverse event. Conclusions: LVRC treatment was safe and effective in patients with nonsevere chronic hypercapnic respiratory failure. It led not only to an improvement in lung function but also to a significant decrease in PaCO2.

ObjectiveThere is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions.MethodsWe analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy.ResultsAmong the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity (DLCO) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and DLCO was slow and did not differ significantly between patients with or without antifibrotic therapy.ConclusionsSurvival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and DLCO.

Background Chronic inflammation emerges as a feature of the pathogenesis of pulmonary arterial hypertension (PAH) in experimental models. Alterations of circulating cell subsets have been observed in patients with PAH. We aimed to assess associations of the white blood cell count with disease severity and outcome in patients with PAH. Methods The total and differential white blood cell count was related to functional parameters, pulmonary hemodynamics and transplantation-free survival in 77 patients with PAH in an observational single center study. Results An increased neutrophil/lymphocyte ratio was associated with poor World Health Organization functional class and shorter 6-minute walking distance, as well as with elevated right atrial pressure and high level of N-terminal prohormone of brain natriuretic peptide. During a median follow-up period of 31 months (range 16-56) 23 patients died and 2 patients were referred to lung transplantation. Using uni- and subsequent bivariate Cox proportional hazards analyses an increased neutrophil/lymphocyte ratio was associated with unfavorable transplantation-free survival independent of hemodynamic parameters and C-reactive protein. The prognostic implication sustained in subsets of patients with incident PAH and in the absence of cardiovascular risk factors. Conclusions The results of this analysis indicate that a neutrophilic inflammation may be associated with clinical deterioration and poor outcome in patients with PAH. Assessing the composition of the differential white blood cell count may render prognostic information and could represent a step towards incorporating an inflammatory marker into the clinical management of patients with PAH. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0407-5) contains supplementary material, which is available to authorized users.

Background Exercise training positively influences exercise tolerance and functional capacity of patients with idiopathic pulmonary arterial hypertension (IPAH). However, the underlying mechanisms are unclear. We hypothesized that exercise modulates the activated inflammatory state found in IPAH patients. Methods Single cardiopulmonary exercise testing was performed in 16 IPAH patients and 10 healthy subjects. Phenotypic characterization of peripheral blood mononuclear cells and circulating cytokines were assessed before, directly after and 1 h after exercise. Results Before exercise testing, IPAH patients showed elevated Th2 lymphocytes, regulatory T lymphocytes, IL-6, and TNF-alpha, whilst Th1/Th17 lymphocytes and IL-4 were reduced. In IPAH patients but not in healthy subject, exercise caused an immediate relative decrease of Th17 lymphocytes and a sustained reduction of IL-1-beta and IL-6. The higher the decrease of IL-6 the higher was the peak oxygen consumption of IPAH patients. Conclusions Exercise seems to be safe from an immune and inflammatory point of view in IPAH patients. Our results demonstrate that exercise does not aggravate the inflammatory state and seems to elicit an immune-modulating effect in IPAH patients.

Introduction: Perivascular inflammation and elevated levels of circulating cytokines are observed in patients idiopathic pulmonary arterial hypertension (IPAH) suggesting a potential role of inflammation and autoimmunity in the pathogenesis. Physical exercise exerts an anti-inflammatory effect in chronic cardiovascular diseases by amelioration of low-grade chronic inflammation. Methods: Patients with IPAH in WHO functional class II-III, without past or current malignant or autoimmune disease and with a current c-reactive protein level < 5 mg/dl were included. Cardiopulmonary exercise testing (CPET) was performed in patients and age-, gender- and body mass index-matched healthy subjects. Phenotypic characterization of lymphocytes was performed with multicolor flow cytometry. Results: Prior to exercise higher levels of CXCR3−/CCR6−/CCR4+ TH2 (p=0.035) and CD25high/CD127low T regulatory lymphocytes (p=0.041) as well as lower levels CXCR3+/CCR6+/CCR4− TH1/TH17 lymphocytes (p=0.007) were found in IPAH patients (n=12) compared to healthy controls (n=10). Overall, CPET provoked a transient elevation of lymphocyte number (p

Background Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. Methods The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined. Results In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura. Conclusion The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.

Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined. In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura. The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.