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 (VAS_cough) 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 VAS_cough 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 VAS_cough (p = 0.047). Long-term follow up identified VAS_cough (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 VAS_cough 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.

Riociguat is licensed for the therapy of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to investigate whether age and comorbidities influence its tolerability and efficacy. Retrospectively, we analyzed data of tolerability, non-invasive, and invasive efficacy at baseline and follow up (FU) of all patients with CTEPH treated with riociguat at the Department of Internal Medicine V, University of Munich (n = 47), grouping patients according to age (<65 versus 65–79 versus ≥80 years) and risk factors for heart failure with preserved ejection fraction (HFpEF) (80 years reported side effects more frequently (40%) than the other age groups (23% and 21% for patients <65 years and patients 65–79, respectively). Cessation of riociguat was rare and occurred independent of age. When looking at the total cohort of 47 patients, three patients stopped therapy and three patients had a reduced maintenance dosage, while 41/47 (87%) and all octogenarians reached the highest maintenance dosage of 7.5 mg/d. The frequency of any side effect was similar in patients in both risk factor groups, and hypotension was only observed in those with <2 risk factors. Parameters of efficacy improved significantly under riociguat treatment. Improvement in 6-min walk distance (6 mwd), N-terminal pro brain natriuretic peptide (Nt-proBNP) and hemodynamics did not differ between age or risk factor groups. In this small real-life cohort, riociguat was well-tolerated and effective in advanced age and risk factors for HFpEF.

Background: Small-cell lung cancer (SCLC) is a highly aggressive tumor, and overall survival (OS) remains poor despite intensive efforts to develop new treatment strategies. In second line, topotecan is the only approved drug, with a median OS of 5.9 months. However, real-world SCLC patients are often in worse condition and harbor more comorbidities than study populations. Therefore, the real-world performance of topotecan may differ from that seen in studies. Here, we analyzed outcomes of SCLC patients receiving topotecan and identified predictive and prognostic markers. Patients and Methods: We retrospectively analyzed 44 consecutive SCLC patients receiving topotecan between 2015 and 2022. We analyzed baseline characteristics (age, ECOG-PS, topotecan cycles, and dosage) and pre-treatment blood values (LDH, CRP, sodium) as well as prognostic scores (neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (TLR), Glasgow Prognostic Score, prognostic nutritional score, systemic inflammation index (SII), and the prognostic index) extracted from electronic patients’ charts to identify predictive and prognostic markers. Results: In our cohort, mPFS and mOS were only 1.9 and 5.6 months, respectively. Gender, ECOG-PS, active brain metastases, NLR, GPS, PNI, and SII significantly influenced PFS and OS in univariate analysis. ECOG-PS (p > 0.001), active brain metastases (p = 0.001), and SII (p = 0.008) were significant independent prognostic variables in a multivariate COX regression model. Selecting patients by these three markers achieved an mPFS of 5.7 months and thus increased the mPFS three-fold. Patients not meeting all criteria had an mPFS of 1.8 months (p = 0.006). Patients identified by prognostic markers had an mOS of 9.1 months (p = 0.002). Conclusions: The efficacy of topotecan in SCLC real-world patients is poor, indicating that many patients were treated without any benefit. Easy-to-obtain markers can predict response and treatment efficacy and should therefore be validated in larger cohorts to identify patients who are more likely to benefit from topotecan.

Immunosuppressants and antifibrotics are currently used to treat patients with various interstitial lung diseases, which may undergo lung transplantation (LTx). The retrospective study aimed to evaluate the potential effects of therapeutic regimen on the perioperative course in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) undergoing LTx. All patients with IPF and PPF undergoing LTx between January 2014 and December 2021 were included. We retrospectively screened for previous use of immunosuppressants and antifibrotic therapy. We analyzed perioperative courses, short-term outcomes, and safety retrospectively. In total, 286 patients with diagnosis of IPF or PPF were analyzed. According to the treatment regimen before LTx, the study cohort was divided into four groups and compared. No differences between antifibrotic monotherapy, combined antifibrotic and immunosuppressive therapy with regard to postoperative complications were observed. Length of mechanical ventilation was shorter in patients with antifibrotics prior to LTx. Pretreatment with antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy, lower body mass index (BMI) and lower blood loss, were independently associated with primary graft dysfunction grades 0–3 72 hours after LTx (p < 0.001). Finally, patients with antifibrotic monotherapy developed significantly less de novo donor-specific antibodies (DSA) (p = 0.009). Higher intraoperative blood loss, etiology of interstitial lung disease (ILD) and older age were independently associated with shorter survival after LTx. Use of antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy in IPF/PPF patients undergoing LTx, proved to be safe and might lead to beneficial effects after LTx.

Background.: Subnormal lung function after lung transplantation (LTx) has increasingly been recognized as an independent risk factor for mortality. Historically, baseline lung allograft dysfunction (BLAD) has been defined using the fixed “< 80% predicted” threshold from population-wide reference equations, which disregards age- and sex-related variability in spirometric values and can lead to systematic overdiagnosis, particularly in older and female recipients. While the lower limit of normal (LLN), derived from Global Lung Initiative reference equations, has been accepted as technical standard in spirometry, it has not yet been applied to define BLAD. Methods.: A retrospective multicenter study included LTx recipients transplanted between 2014 and 2018. Lung function trajectories and allograft survival were followed-up until August 2024. The association of BLAD defined by forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) < LNN as time-dependent variable with graft loss was studied using time-dependent Cox proportional hazard models. Results.: We analyzed 726 patients after LTx including 102 unilateral LTx recipients, of whom 470 (65%) of the cohort achieved normal baseline lung function defined as FEV1 and FVC ≥ LLN. Two hundred thirty-six patients experienced graft loss (n = 2 redo LTx) and 179 developed chronic lung allograft dysfunction. After adjusting for age, disease, transplant type, and chronic lung allograft dysfunction, baseline FEV1 or FVC < LLN was associated with graft loss (hazard ratio, 1.822; 95% confidence interval, 1.372-2.418; P < 0.001). Conclusions.: BLAD defined by concurrent baseline FEV1 or FVC below the LLN was strongly associated with increased risk of graft loss. These findings extend prior studies that used the fixed 80% threshold by demonstrating that an LLN-based, age- and sex-adjusted definition of BLAD identifies lung transplant recipients at risk, thereby avoiding fixed cutoff associated age- and sex-bias.

Background: Lung cancer metastasis results from local invasion, loss of adhesion, migration, and distant implantation. Some small tumors metastasize diffusely other tumors progress to local bulky disease without metastasis. Here we compare these biologically divergent courses of progression and present an analysis of clinical features related to early diffuse metastasis vs. bulky disease. Methods: We retrospectively collected data from pathologically confirmed not-metastatic “bulky” (cT3-T4cN0cM0) or “diffusely metastatic” (cT1-T2cN1-3cM1) patients with lung cancer treated at our center from 2013 to 2023. Clinical data including sex, age, histology, ECOG-PS, tumor stage, smoking status, presence, and site of metastases, LDH, CRP, NLR ratio were collected. Results: A total of 375 patents with “bulky” (n = 95) or diffusely metastatic lung cancer (n = 280) were included in the analysis. In the univariate analysis, the diffusely metastatic population was younger (p = 0.001), had a higher proportion of never smokers (p = 0.02), histologically adenocarcinoma (p < 0.0001), TTF1 positive (p < 0.00001) and elevated baseline LDH in serum (LDH > 250U/l, p < 0.0001) compared to “bulky” population. Patients with diffuse metastatic disease presented worse OS (HR = 2.34, p = 0.0001) and PFS (HR = 6.89, p < 0.0001) compared to patients with bulky disease. Conclusions: Younger age, never smokers, TTF1 positivity, poorly differentiated tumors, adenocarcinoma histology were independently associated with risk of distant metastasis.