INTRODUCTION:Sex-related differences in interstitial lung disease (ILD) phenotypes are well recognized, but it remains unclear whether sex itself independently influences outcomes in non-idiopathic pulmonary fibrosis (non-IPF) ILD once comorbidities, lung function, and treatment are considered. METHODS:In the prospective INSIGHTS-ILD registry (data cut 17 September 2025), we compared men and women with non-IPF ILD using descriptive analyses and Cox models with prespecified adjustment steps: model A (age, comorbidity count, and smoking), model B (A + forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]), and model C (B + antifibrotic therapy). Prespecified subgroup analyses included age strata (≤55 and >55 years) and ILD entities. Longitudinal FVC and DLCO trajectories were assessed over 24 months. RESULTS:Among 883 patients (483 men and 400 women), exposures and disease entities differed significantly by sex: men reported more occupational/environmental exposures and had higher rates of fibrotic idiopathic interstitial pneumonia, whereas women more frequently had autoimmune-related ILD and a family history of ILD. Men had a higher comorbidity burden and more often received antifibrotic therapy at baseline. Survival was shorter in men (HR: 1.51; 95% CI: 1.03-2.21), but this association disappeared after adjustment in model A (HR: 1.04; 95% CI: 0.65-1.68), model B (HR: 1.03; 95% CI: 0.61-1.74), and model C (HR: 1.04; 95% CI: 0.62-1.77). Progression-free survival and transplant-free survival showed no consistent sex-related differences. Longitudinal FVC and DLCO declines were modest and largely parallel in both sexes, with no significant between-group differences. Findings were similar across age groups and ILD entities. CONCLUSION:Men and women with non-IPF ILD differ in exposures, phenotypes, and comorbidities, but after accounting for these factors, sex is not an independent predictor of survival or functional progression. Risk assessment should therefore primarily be based on objective disease characteristics rather than sex alone.

Die Anti-MDA5-positive Dermatomyositis stellt einen seltenen Subtyp der idiopathisch inflammatorischen Myopathien dar, die sich durch eine rasch progrediente interstitielle Lungenbeteiligung und schwerwiegende kutane Ulzerationen auszeichnet, und ist mit einer hohen Mortalität verbunden. Das gleichzeitige Auftreten einer Sarkoidose mit Multisystembeteiligung einer Myositis ist in der Literatur bisher nur extrem selten beschrieben worden. Wir berichten über den Fall eines 39-jähriger Mannes mit einer seit 3 Jahren bekannten Anti-MDA-5-positiven Dermatomyositis, der unter sukzessiver Reduktion der immunsuppressiven Therapie eine subjektive Verschlechterung der Dyspnoe sowie eine Hyperkalzämie mit akuter Nierenschädigung und deutlicher Allgemeinzustandsverschlechterung entwickelte. Mittels Bronchoskopie und Lymphknotenbiopsie konnte letztlich die Diagnose einer Sarkoidose gesichert werden. Der vorliegende Fallbericht verdeutlicht die Wichtigkeit, im Krankheitsverlauf einer seltenen Erkrankung die Diagnose bei neu aufgetretenen Symptomen kontinuierlich zu reevaluieren. Beim Vorliegen einer ausgeprägten Lymphadenopathie, einer neu aufgetretenen Hyperkalzämie und für eine Dermatomyositis atypischen Lungenparenchymveränderungen sollte somit auch an die Differenzialdiagnose einer Sarkoidose gedacht werden.

Case presentationDescription of a patient with a progressive destructive lung disease resembling pleuroparenchymal fibroelastosis, liver cirrhosis and bone marrow changes. Genetic workup identified a rare heterozygous coding variant in the TERT (telomerase reverse transcriptase) gene c.472 C>T; p.(Leu158Phe) and telomere length testing revealed significant telomere shortening, supporting the diagnosis of telomere biology disorder (TBD).DiscussionTBD is an underrecognized cause of interstitial lung disease (ILD). It is a heterogeneous disease that can affect different organs, including lungs, liver and bone marrow. Genetic testing in ILD is crucial for early diagnosis, risk assessment, and family screening. Identifying this variant enables targeted genetic testing for relatives, allowing preventive measures and lifestyle modifications.

Background: Anti-MDA5 positive dermatomyositis is a rare subtype of idiopathic inflammatory myopathies often accompanied by rapidly progressive interstitial lung disease and severe cutaneous ulcerations. It is associated with a high mortality. The simultaneous occurrence of sarcoidosis with multisystemic involvement of myositis has only been described very rarely in the literature to date. Case report: We report the case of a 39-year-old man with a 3-year history of anti-MDA-5 positive dermatomyositis who developed a worsening of dyspnea and hypercalcemia with acute kidney injury and a marked deterioration in his general condition after successive reductions in immunosuppressive therapy. A bronchoscopy and lymph node biopsy ultimately confirmed the diagnosis of sarcoidosis. Conclusion: This case report illustrates the importance of continuously re-evaluating the diagnosis when new symptoms occur during the course of a rare disease. In the presence of pronounced lymphadenopathy, new hypercalcemia and lung parenchymal changes atypical for dermatomyositis, the differential diagnosis of sarcoidosis should also be considered.

Journal Article Corrected proof Daratumumab as rescue therapy in life-threatening granulomatosis with polyangiitis Get access Martin Krusche, Martin Krusche III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Correspondence to: Martin Krusche, Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20251 Hamburg, Germany. E-mail: m.krusche@uke.de https://orcid.org/0000-0002-0582-7790 Search for other works by this author on: Oxford Academic PubMed Google Scholar Tim Oqueka, Tim Oqueka II Department of Medicine for Oncology and Pulmonology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Dominic Wichmann, Dominic Wichmann Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefan Kluge, Stefan Kluge Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany https://orcid.org/0000-0001-8391-3988 Search for other works by this author on: Oxford Academic PubMed Google Scholar Tobias B Huber, Tobias B Huber III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Ina Kötter, Ina Kötter III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Schmidt-Lauber Christian Schmidt-Lauber III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyResearch Center On Rare Kidney Diseases (RECORD), University Hospital Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, kead474, https://doi.org/10.1093/rheumatology/kead474 Published: 09 September 2023 Article history Accepted: 29 August 2023 Published: 09 September 2023 Corrected and typeset: 23 September 2023

Rationale: Telemonitoring of lung function and symptoms might help to identify exacerbations to prevent hospitalizations. We investigated the acceptance and usability of telemonitoring in COPD patients. Methods: In this prospective multicentre study we used home-based spirometry, accelerometry, a smartphone-based disease-control interface (DCI) for symptoms: CAT questionnaire, need for rescue inhaler. We evaluated individual changes of FEV1 beyond day-to-day variability, steps, change in CAT score, rescue inhaler use for 12 months follow-up after exacerbation Results: 43 patients (n=43; mean age, 65±7 years; mean FEV1%, 42± 14) were enrolled. Adherence to home-based spirometry, DCI and accelerometry was 247, 252 and 58 days, respectively. We found a good agreement between in-clinic and home-based spirometry (Bland–Altman: mean difference 111 ml; 95% limits of agreement: −506 to 782 ml). In patients with exacerbation during follow-up (n=17), home-based spirometry revealed a mean decline of 152 ml in FEV1 vs. stable FEV1 (+22 ml) in those without exacerbation, (p=0.056). Changes in home-based FEV1 showed a stronger correlation with time to first exacerbation and number of exacerbations (correlation coefficients 0.38 and -0.25) than in-clinic based-FEV1. There was a good correlation between both components of DCI (R=0.36, p=0.044). Clinically relevant changes in FEV1 and DCI could be observed 5 days right before and during exacerbations. Conclusion: In adherent COPD patients home-based telemonitoring provides plausible and reliable changes of symptoms and lung function that might allow an early intervention.

Melanoma differentiation-associated gene 5 (MDA5) positive dermatomyositis is a rare systemic autoimmune disease that is associated with life-threatening rapidly progressive interstitial lung disease. We report the case of a 19-year-old male patient with a life-threatening disease course caused by rapidly progressive interstitial lung disease that caused respiratory failure despite intensive immunosuppression with multiple agents (steroids, IV immunoglobulins, tofacitinib, cyclophosphamide, mycophenolate mofetil, ciclosporin and rituximab). Rescue therapy with daratumumab, an anti-CD38-antibody, was initiated. Significant pulmonary improvement was noticed after 4 weekly injections of 1,800 mg. After 6 months of follow up, stable disease remission with significant pulmonary improvement and persistent depletion of CD38 thorn plasma cells and MDA5-antibody titers were seen. This is the first report of the successful use of daratumumab in dermatomyositis. It highlights the potential of CD38 targeted therapies for severe antibody-mediated autoimmune diseases such as dermatomyositis. CHEST 2023; 163(1):e1-e5

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 P-0.1, inspiratory muscle strength (PImax) and total respiratory muscle strain (P-0.1/PImax) in addition to standard pulmonary functions tests, capillary blood gas analysis, 6 min walking tests and functional questionnaires. Results Pathological P-0.1/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 P-0(.1) was pathologically increased in both groups. Increased P-0(.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 P-0.1, PImax or P-0.1/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.

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.

Introduction Since 2019, immunotherapy of chronic rhinosinusitis with polyposis nasi (CRSwNP) has been established as another treatment option. Data on possible interaction potential of the currently approved antibodies (dupilumab, omalizumab) in the context of concurrent immunotherapy with another antibody are underrepresented in the current study landscape. Studies are needed in this regard to ensure optimal therapy even in complicated cases.

BACKGROUND: g-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 METHODS: 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. RESULTS: 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 p < 0.001; 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. CONCLUSION: 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. (c) 2021 International Society for Heart and Lung Transplantation. All rights reserved.

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).

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 < 0.001). Adverse side effects were mostly only mild, and no rescue therapy was needed. 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.

Background: Pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF) can present elevated pulmonary vascular resistance (PVR) suggesting pulmonary vascular disease, but therapeutic consequence is uncertain. Ventilatory inefficiency and decreased blood carbon dioxide tension at rest are common features in patients with pulmonary vascular diseases.Objective: To assess blood carbon dioxide tension at rest in relation to elevated PVR and the effects of treatment with phosphodiesterase type 5 inhibitors (PDE5i) in patients with PH due to HFpEF. Methods: We retrospectively investigated 78 HFpEF patients with either combined post- and pre-capillary PH (Cpc-PH, PVR ≥3 Wood units, n=56) or isolated post-capillary PH (Ipc-PH, PVR <3 Wood units, n=22). 26 HFpEF patients with Cpc-PH received targeted treatment with PDE5i. Results: Blood carbon dioxide tension levels at rest were lower in HFpEF patients with Cpc-PH compared to Ipc-PH (area under the curve [AUC] 0.66, 95%-confidence interval [CI] 0.52- 0.8, P<0.05) and correlated inversely with PVR. In HFpEF patients with Cpc-PH, treatment with a PDE5i for a median of 10 months increased blood carbon dioxide tension levels. Fourteen patients (54%) showed clinical response to treatment with an improvement in WHO functional class and right ventricular function. Levels of blood carbon dioxide tension were lower at baseline in responders compared to non-responders (AUC 0.81, 95%-CI 0.62-0.99, P<0.001).Conclusion: Low blood carbon dioxide tension may indicate the presence and extent of pulmonary vascular disease in patients with HFpEF and may help to select patients with Cpc-PH for targeted therapy.

Einleitung Seit 2019 ist die Immuntherapie der chronischen Rhinosinusitis mit Polyposis nasi (CRSwNP) als weitere Möglichkeit der Behandlung etabliert. Daten zu möglichen Interaktionspotential der aktuell zugelassenen Antikörper (Dupilumab, Omalizumab) im Rahmen einer zeitgleichen Immuntherapie mit einem anderen Antikörper sind in der aktuellen Studienlandschaft unterrepräsentiert. Hierzu bedarf es Studien, um auch bei komplizierten Fällen eine optimale Therapie zu gewährleisten.

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 < 0001) and had fewer comorbidities at baseline with a lower mean overall age-adjusted Charlson Comorbidity Index (mean [SD], 3.0 [2.6] vs 4.0 [2.7]; P < 0.001) than patients with seasonal influenza. COVID-19 patients had a longer duration of hospitalization (mean [SD], 25.9 days [26.6 days] vs 17.2 days [21.0 days]; P = 0.002), a more frequent need for oxygen therapy (101 [60.8%] vs 103 [40.4%]; P < 0.001) and invasive ventilation (52 [31.3%] vs 32 [12.5%]; P < 0.001) and were more frequently admitted to the intensive care unit (70 [42.2%] vs 51 [20.0%]; P < 0.001) than seasonal influenza patients. Among immunocompromised patients, those in the COVID-19 group had a higher hospital mortality compared to those in the seasonal influenza group (13 [33.3%] vs 8 [11.6%], P = 0.01). In conclusion, we show that COVID-19 patients were younger and had fewer baseline comorbidities than seasonal influenza patients but were at increased risk for severe illness. The high mortality observed in immunocompromised COVID-19 patients emphasizes the importance of protecting these patient groups from SARS-CoV-2 infection.

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.