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Abstract Background Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD. Research question We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD. Methods Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses. Results Among 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p

Abstract COVID-19 was a challenge for health-care systems worldwide, causing large numbers of hospitalizations and inter-hospital transfers. We studied whether transfer, as well as its reason, was associated with the duration of hospitalization in non-ICU and ICU patients. For this purpose, all patients hospitalized due to COVID-19 between August 1st and December 31st, 2021, in a network of hospitals in Southern Germany were comprehensively characterized regarding their clinical course, therapy, complications, transfers, reasons for transfer, involved levels of care, total period of hospitalization and in-hospital mortality, using univariate and multiple regression analyses. While mortality was not significantly associated with transfer, the period of hospitalization was. In non-ICU patients (n = 545), median (quartiles) time was 7.0 (4.0–11.0) in non-transferred (n = 458) and 18.0 (11.0–29.0) days in transferred (n = 87) patients (p

Abstract Background Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting. Methods Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes. Results In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p

Abstract As a result of advances in the treatment of lung cancer, the life expectancy of lung cancer patients has improved significantly, but it remains the leading cause of cancer death worldwide. For decades, most of the initial tumor biopsies have been obtained by bronchoscopy or computed tomography (CT)-guided transthoracic lung biopsy without concerning reports of cancer seeding following the latter. In this case report we discuss the patient history of a 56-year old women with low-differentiated squamous cell lung cancer who developed tumor seeding following a CT-guided transthoracic biopsy 11 months after the intervention. This is put into context reviewing former and current literature.

Background: Small cell lung cancer (SCLC) is characterized by aggressive growth and poor prognosis. Although SCLC affects nearly exclusively heavy smokers and leads to frequent respiratory symptoms, the impact of pre-therapeutic lung function testing in SCLC is sparely investigated until now. Therefore, we sought to examine whether we could find prognostic markers in pre-therapeutic lung function testing of SCLC patients. Patients and Methods: We retrospectively analysed a cohort of 205 patients with the diagnosis of SCLC between 2010 and 2018. Pre-therapeutic values of spirometry, body plethysmography and measurement of diffusing capacity was extracted from patients’ charts. Comparisons between groups were performed using the Mann–Whitney U- test or by chi-square tests as appropriate. Kaplan–Meier analyses and COX-regression models were performed to correlate lung function parameters with patients’ outcome. Results: Airway obstruction itself, or the diagnosis chronic obstructive pulmonary disease (COPD) based on GOLD definitions did not correlate with survival in SCLC patients. Hyperinflation measured by increased residual volume and residual volume to total lung capacity ratio (log-rank p

Background: The use of maintenance medication in patients with chronic obstructive pulmonary disease (COPD) in real life is known to deviate from recommendations in guidelines, which are largely based on randomized controlled trials and selected populations. Objectives: We used the COSYCONET ( CO PD and Sy stemic Consequences – Co morbidities Net work) cohort to analyze factors linked to the use of COPD drugs under non-interventional circumstances. Design: COSYCONET is an ongoing, multi-center, non-interventional cohort of patients with COPD. Methods: Patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 0–4 participating in visits 1–5 were included. Data covered the period from 2010 to 2018. Generalized linear models were used to examine the relation of COPD characteristics to different types of respiratory medication. Results: A total of 1043 patients were included. The duration of observation was 4.5 years. Use of respiratory medication depended on GOLD grades 0–4 and groups A-D. Long-acting muscarinic antagonist therapy increased over time, and was associated with low carbon monoxide (CO) diffusing capacity, while inhaled corticosteroid (ICS) use decreased. Active smoking was associated with less maintenance therapy in general, and female sex with less ICS use. From the eight items of the COPD Assessment Test, only hill and stair climbing were consistently linked to treatment. Conclusion: Using data from a large, close to real-life observational cohort, we identified factors linked to the use of various types of respiratory COPD medication. Overall, use was consistent with GOLD recommendations. Beyond this, we identified other correlates of medication use that may help us to understand and improve therapy decisions in clinical practice. Trial registration: ClinicalTrials.gov NCT01245933.

Abstract Introduction Trials of CT‐based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population. Methods We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL). We compared the sensitivity of the following lung cancer screening criteria overall and stratified by age and histology: the National Lung Screening Trial (NLST), the Danish Lung Cancer Screening Trial (DLCST), the 2013 and 2021 US Preventive Services Task Force (USPSTF), and an adapted version of the Prostate, Lung, Colorectal, and Ovarian no race model (adapted PLCOm2012) with 6‐year risk thresholds of 1.0%/6 year and 1.7%/6 year. Results Overall, the adapted PLCOm2012 model (1%/6 years), selected the highest proportion of lung cancer patients for screening (72.4%), followed by the 2021 USPSTF (70.0%), the adapted PLCOm2012 (1.7%/6 year) (57.4%), the 2013 USPTF (57.0%), DLCST criteria (48.7%), and the NLST (48.5%). The adapted PLCOm2012 risk model (1.0%/6 year) had the highest sensitivity for all histological types except for small‐cell and large‐cell carcinomas (non‐significant), whereas the 2021 USPTF selected a higher proportion of patients. The sensitivity levels were higher in males than in females. Conclusion Using a risk‐based selection score resulted in higher sensitivities compared to criteria using dichotomized age and smoking history. However, gender disparities were apparent in all studied eligibility criteria. In light of increasing lung cancer incidences in women, all selection criteria should be reviewed for ways to close this gender gap, especially when implementing a large‐scale lung cancer screening program.

Abstract In chronic obstructive pulmonary disease (COPD), comorbidities and worse functional status predict worse outcomes, but how these predictors compare with regard to different outcomes is not well studied. We thus compared the role of cardiovascular comorbidities for mortality and exacerbations. Data from baseline and up to four follow-up visits of the COSYCONET cohort were used. Cox or Poisson regression was employed to determine the relationship of predictors to mortality or mean annual exacerbation rate, respectively. Predictors comprised major comorbidities (including cardiovascular disease), lung function (forced expiratory volume in 1 s [FEV1], diffusion capacity for carbon monoxide [TLCO]) and their changes over time, baseline symptoms, exacerbations, physical activity, and cardiovascular medication. Overall, 1817 patients were included. Chronic coronary artery disease (p = 0.005), hypertension (p = 0.044) and the annual decline in TLCO (p = 0.001), but not FEV1 decline, were predictors of mortality. In contrast, the annual decline of FEV1 (p = 0.019) but not that of TLCO or cardiovascular comorbidities were linked to annual exacerbation rate. In conclusion, the presence of chronic coronary artery disease and hypertension were predictors of increased mortality in COPD, but not of increased exacerbation risk. This emphasizes the need for broad diagnostic workup in COPD, including the assessment of cardiovascular comorbidity. Clinical Trials: NCT01245933.

Abstract In patients with COPD, it has not been comprehensively assessed whether the predictive value of comorbidities for mortality differs between men and women. We therefore aimed to examine sex differences of COPD comorbidities in regard with prognosis by classifying comorbidities into a comorbidome related to extrapulmonary disorders and a pulmorbidome, referring to pulmonary disorders. The study population comprised 1044 women and 1531 men with the diagnosis of COPD from COSYCONET, among them 2175 of GOLD grades 1–4 and 400 at risk. Associations of comorbidities with mortality were studied using Cox regression analysis for men and women separately. During the follow-up (median 3.7 years) 59 women and 159 men died. In men, obesity, hypertension, coronary artery disease, liver cirrhosis, osteoporosis, kidney disease, anaemia and increased heart rate (HR) predict mortality, in women heart failure, hyperuricemia, mental disorders, kidney disease and increased HR (p

Background: Evidence suggests differences in ventilation efficiency and respiratory mechanics between early COVID-19 pneumonia and classical acute respiratory distress syndrome (ARDS), as measured by established ventilatory indexes, such as the ventilatory ratio (VR; a surrogate of the pulmonary dead-space fraction) or mechanical power (MP; affected, e.g., by changes in lung-thorax compliance). Objectives: The aim of this study was to evaluate VR and MP in the late stages of the disease when patients are ready to be liberated from the ventilator after recovering from COVID-19 pneumonia compared to respiratory failures of other etiologies. Design: A retrospective observational cohort study of 249 prolonged mechanically ventilated, tracheotomized patients with and without COVID-19-related respiratory failure. Methods: We analyzed each group’s VR and MP distributions and trajectories [repeated-measures analysis of variance (ANOVA)] during weaning. Secondary outcomes included weaning failure rates between groups and the ability of VR and MP to predict weaning outcomes (using logistic regression models). Results: The analysis compared 53 COVID-19 cases with a heterogeneous group of 196 non-COVID-19 subjects. VR and MP decreased across both groups during weaning. COVID-19 patients demonstrated higher values for both indexes throughout weaning: median VR 1.54 versus 1.27 ( p

Abstract We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p

Abstract Background The novel coronavirus SARS-CoV-2 has caused a global COVID-19 pandemic, leading to worldwide changes in public health measures. In addition to changes in the public sector (lockdowns, contact restrictions), hospitals modified care to minimize risk of infection and to mobilize resources for COVID-19 patients. Our study aimed to assess the impact of these measures on access to care and behaviour of patients with thoracic malignancies. Methods Thoracic oncology patients were surveyed in October 2020 using paper-based questionnaires to assess access to ambulatory care services and tumor-directed therapy during the COVID-19 pandemic. Additionally, behaviour regarding social distancing and wearing of face masks were assessed, as well as COVID-19 exposure, testing and vaccination. Results are presented as absolute and relative frequencies for categorical variables and means with standard deviation for numerical variables. We used t-test, and ANOVA to compare differences in metric variables and Chi2-test to compare proportions between groups. Results 93 of 245 (38%) patients surveyed completed the questionnaire. Respiration therapy and physical therapy were unavailable for 57% to 70% of patients during March/April. Appointments for tumor-directed therapy, tumor imaging, and follow-up care were postponed or cancelled for 18.9%, 13.6%, and 14.8% of patients, respectively. Patients reported their general health as mostly unaffected. The majority of patients surveyed did not report reducing their contacts with family. The majority reduced contact with friends. Most patients wore community masks, although a significant proportion reported respiratory difficulties during prolonged mask-wearing. 74 patients (80%) reported willingness to be vaccinated against SARS-CoV-2. Conclusions This survey provides insights into the patient experience during the second wave of the COVID-19 pandemic in Munich, Germany. Most patients reported no negative changes to cancer treatments or general health; however, allied health services were greatly impacted. Patients reported gaps in social distancing, but were prepared to wear community masks. The willingness to get vaccinated against SARS-CoV-2 was high. This information is not only of high relevance to policy makers, but also to health care providers.

Background: Chest computed tomography (CT) is increasingly used for phenotyping and monitoring of patients with COPD. The aim of this work was to evaluate the association of Pi10 as a measure of standardized airway wall thickness on CT with exacerbations, mortality, and response to triple therapy. Methods: Patients of GOLD grades 1–4 of the COSYCONET cohort with prospective CT scans were included. Pi10 was automatically computed and analyzed for its relationship to COPD severity, comorbidities, lung function, respiratory therapy, and mortality over a 6-year period, using univariate and multivariate comparisons. Results: We included n = 433 patients (61%male). Pi10 was dependent on both GOLD grades 1–4 ( p = 0.009) and GOLD groups A–D ( p = 0.008); it was particularly elevated in group D, and ROC analysis yielded a cut-off of 0.26 cm. Higher Pi10 was associated to lower FEV 1 % predicted and higher RV/TLC, moreover the annual changes of lung function parameters ( p

BackgroundChronic obstructive pulmonary disease (COPD) collectively refers to chronic and progressive lung diseases that cause irreversible limitations in airflow. Patients with COPD are at high risk for severe respiratory symptoms upon influenza virus infection. Airway epithelial cells provide the first-line antiviral defense, but whether or not their susceptibility and response to influenza virus infection changes in COPD have not been elucidated. Therefore, this study aimed to compare the susceptibility of COPD- and control-derived airway epithelium to the influenza virus and assess protein changes during influenza virus infection by quantitative proteomics.Materials and methodsThe presence of human- and avian-type influenza A virus receptor was assessed in control and COPD lung sections as well as in fully differentiated primary human bronchial epithelial cells (phBECs) by lectin- or antibody-based histochemical staining. PhBECs were from COPD lungs, including cells from moderate- and severe-stage diseases, and from age-, sex-, smoking, and history-matched control lung specimens. Protein profiles pre- and post-influenza virus infection in vitro were directly compared using quantitative proteomics, and selected findings were validated by qRT-PCR and immunoblotting.ResultsThe human-type influenza receptor was more abundant in human airways than the avian-type influenza receptor, a property that was retained in vitro when differentiating phBECs at the air–liquid interface. Proteomics of phBECs pre- and post-influenza A virus infection with A/Puerto Rico/8/34 (PR8) revealed no significant differences between COPD and control phBECs in terms of flu receptor expression, cell type composition, virus replication, or protein profile pre- and post-infection. Independent of health state, a robust antiviral response to influenza virus infection was observed, as well as upregulation of several novel influenza virus-regulated proteins, including PLSCR1, HLA-F, CMTR1, DTX3L, and SHFL.ConclusionCOPD- and control-derived phBECs did not differ in cell type composition, susceptibility to influenza virus infection, and proteomes pre- and post-infection. Finally, we identified novel influenza A virus-regulated proteins in bronchial epithelial cells that might serve as potential targets to modulate the pathogenicity of infection and acute exacerbations.

Abstract Background Lung emphysema is an important phenotype of chronic obstructive pulmonary disease (COPD), and CT scanning is strongly recommended to establish the diagnosis. This study aimed to identify criteria by which physicians with limited technical resources can improve the diagnosis of emphysema. Methods We studied 436 COPD patients with prospective CT scans from the COSYCONET cohort. All items of the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale, as well as data from spirometry and CO diffusing capacity, were used to construct binary decision trees. The importance of parameters was checked by the Random Forest and AdaBoost machine learning algorithms. Results When relying on questionnaires only, items CAT 1 & 7 and SGRQ 8 & 12 sub-item 3 were most important for the emphysema- versus airway-dominated phenotype, and among the spirometric measures FEV1/FVC. The combination of CAT item 1 (≤ 2) with mMRC (> 1) and FEV1/FVC, could raise the odds for emphysema by factor 7.7. About 50% of patients showed combinations of values that did not markedly alter the likelihood for the phenotypes, and these could be easily identified in the trees. Inclusion of CO diffusing capacity revealed the transfer coefficient as dominant measure. The results of machine learning were consistent with those of the single trees. Conclusions Selected items (cough, sleep, breathlessness, chest condition, slow walking) from comprehensive COPD questionnaires in combination with FEV1/FVC could raise or lower the likelihood for lung emphysema in patients with COPD. The simple, parsimonious approach proposed by us might help if diagnostic resources regarding respiratory diseases are limited. Trial registration ClinicalTrials.gov, Identifier: NCT01245933, registered 18 November 2010, https://clinicaltrials.gov/ct2/show/record/NCT01245933 .

Background: The COVID-19 vaccines, face masks, and social distancing are effective interventions to prevent SARS-CoV-2 infections. In this study, we aimed to determine lung cancer patients’ attitudes toward vaccination, changes in behavior after vaccination, and willingness to continue mask wearing after the pandemic. Methods: We sent out questionnaires to 220 thoracic oncology patients treated at our lung cancer center in May 2021. The questionnaire focused on patients’ vaccination status, self-reported experiences surrounding vaccination, and assessed changes in behaviors before and after vaccination as well as opinions toward mask wearing after the pandemic. Results are presented as absolute and relative frequencies and means with standard deviation and compared using t test, paired t test, and analysis of variance test as well as chi 2 test, and Fisher exact text. Results: About 91.0% of patients reported having received at least 1 vaccination. About 73.3% of patients reported having at least 1 reaction to the vaccination. The most common reactions were pain at the injection site, fatigue, and headache. After vaccination, patients increased contact with family and friends, use of public transport, and grocery shopping. Overall, the level of willingness to wear masks beyond the end of the pandemic differed according to vaccination status. Conclusions: Acceptance of the COVID-19 vaccination among thoracic oncology patients in Germany was high. Overall, patients with thoracic malignancies tolerated the COVID-19 vaccination well. Rate of adverse reaction was not higher compared with the general population. After the vaccination, patients increased social contacts and usage of public transport. These changes suggest positive psychological effects on quality of life. While reducing social distancing can increase the risk of infection, our results indicate that an extension of mask mandates after the pandemic would likely be accepted by a majority of thoracic oncology patients, suggesting that our cohort was still aware and in support of other measure of protection.

Abstract Treatment with single agent immune checkpoint inhibitors (ICIs) has tremendously changed second line therapy in NSCLC. However, there are still no reliable biomarkers predicting response and survival in this group of patients. PD-L1 revealed to be a correlating, but no perfect marker. Therefore, we sought to investigate in this prospective study, whether inflammation status and cytokine profile could serve as additional biomarkers guiding treatment decision for single agent ICIs in NSCLC. 29 stage IV NSCLC patients receiving single agent PD-1 checkpoint-inhibitor in second line were prospectively enrolled. Inflammatory scores and cytokine profiles (IL-6, IL-8, IL-10, IFN-γ and TNFα) have been obtained before treatment and at the time of the first staging. Cytokine profiles were correlated with response and survival. Patients with signs of pre-therapeutic inflammation (elevated, NLR, SII, IL-6, IL-8) showed significantly lower response to ICI treatment and reduced PFS. Contrary, elevated levels of IFN-γ revealed to characterize a subgroup of patients, who significantly benefits from ICI treatment. Furthermore, low systemic inflammation and high levels of IFN-γ characterized patients with long term-response to ICI treatment. Pre-therapeutic assessment of inflammation and cytokine profiles has the ability to predict response and survival in NSCLC patients treated with single agent ICIs.

Abstract Background Forced expiratory volume in one second (FEV1) characterizes the pathophysiology of COPD and different trajectories of FEV1 decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV1 and change in disease-specific and generic HRQL. Methods We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George’s Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV1 and to calculate mean changes in HRQL per FEV1 change categories [decrease (≤ − 100 ml), no change, increase (≥ 100 ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV1 difference or change. Results We observed a statistically significant deterioration in SGRQ (total score + 1.3 units) after 3 years, which was completely driven by the activity component (+ 4 units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV1, 28% were recorded as no change in FEV1, and 13% experienced an increase. The relationship between HRQL and FEV1 was found to be approximately linear with decrease in FEV1 being statistically significantly associated with a deterioration in SGRQ (+ 3.20 units). Increase in FEV1 was associated with improvements in SGRQ (− 3.81 units). The associations between change in FEV1 and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV1 and the SGRQ activity domain. Conclusions Difference and change in FEV1 over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes. Trial registration NCT01245933 . Date of registration: 18 November 2010.

Abstract Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL). Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL. DemTect scores were =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment. We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.

Background: Infection control measures for coronavirus disease 2019 (COVID-19) might have affected management and clinical state of patients with COPD. We analysed to which extent this common notion is fact-based. Methods: Patients of the COSYCONET cohort were contacted with three recurring surveys (COVID1, 2 and 3 at 0, 3 and 6 months, respectively). The questionnaires comprised behaviour, clinical and functional state, and medical treatment. The responses to the questionnaires were compared amongst themselves and with pre-COVID information from the last visit of COSYCONET. Results: Overall, 594 patients were contacted and 375 patients (58% males, forced expiratory volume in 1 s (FEV1) 61±22% predicted) provided valid data in COVID1 and COVID2. Five patients reported infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most patients – except for patients with higher education – reported compliance with recommended protective measures, whereby compliance to hygiene, contact and access to physicians slightly improved between COVID1 and COVID2. Also, patients obtained more information from physicians than from public media. In the majority of cases, the personal physician could not be substituted by remote consultation. Over time, symptoms slightly increased and self-assessed physical capacity decreased. Results of COVID3 were similar. Women and patients with more exacerbations and dyspnoea avoided medical consultations, whereas Global Initiative for Chronic Obstructive Lung Disease (GOLD) D patients were more amenable to tele-consultation. Conclusion: In well-characterised COPD patients, we observed on average slight deteriorations of clinical state during the period of COVID-19 restrictions, with high and partially increasing adherence to protective measures. The data suggest that in particular, women and GOLD D patients should be actively contacted by physicians to identify deteriorations.

Osimertinib is a third-generation tyrosine kinase inhibitor that became the preferred first-line treatment option for metastatic non-small cell lung cancer with sensitizing epidermal growth factor receptor mutations. Drug-induced pneumonitis is known to occur with osimertinib. In case of severe pneumonitis, discontinuation of treatment and therapy with corticosteroids is recommended, and a treatment switch is usually performed. We herein report the treatment course in three patients who were rechallenged with osimertinib under steroid protection following an osimertinib-induced pneumonitis. All our patients were initially re-exposed to a lower dose of osimertinib. Two patients were successfully rechallenged under prednisolone protection. The third patient, who was initially retreated with osimertinib without steroid protection, suffered from a recurrent pneumonitis, and was later rechallenged successfully under steroid protection. Our case series indicates that rechallenge with osimertinib following recovery from osimertinib-induced pneumonitis allows a successful rechallenge in individual cases when alternative treatment options are lacking. Concomitant steroids appear to protect against flares of pneumonitis during rechallenge.

Abstract Background COPD influences cardiac function and morphology. Changes of the electrical heart axes have been largely attributed to a supposed increased right heart load in the past, whereas a potential involvement of the left heart has not been sufficiently addressed. It is not known to which extent these alterations are due to changes in lung function parameters. We therefore quantified the relationship between airway obstruction, lung hyperinflation, several echo- and electrocardiographic parameters on the orientation of the electrocardiographic (ECG) P, QRS and T wave axis in COPD. Methods Data from the COPD cohort COSYCONET were analyzed, using forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), left ventricular (LV) mass, and ECG data. Results One thousand, one hundred and ninety-five patients fulfilled the inclusion criteria (mean ± SD age: 63.9 ± 8.4 years; GOLD 0–4: 175/107/468/363/82). Left ventricular (LV) mass decreased from GOLD grades 1–4 (p = 0.002), whereas no differences in right ventricular wall thickness were observed. All three ECG axes were significantly associated with FEV1 and FRC. The QRS axes according to GOLD grades 0–4 were (mean ± SD): 26.2° ± 37.5°, 27.0° ± 37.7°, 31.7° ± 42.5°, 46.6° ± 42.2°, 47.4° ± 49.4°. Effects of lung function resulted in a clockwise rotation of the axes by 25°-30° in COPD with severe airway disease. There were additional associations with BMI, diastolic blood pressure, RR interval, QT duration and LV mass. Conclusion Significant clockwise rotations of the electrical axes as a function of airway obstruction and lung hyperinflation were shown. The changes are likely to result from both a change of the anatomical orientation of the heart within the thoracic cavity and a reduced LV mass in COPD. The influences on the electrical axes reach an extent that could bias the ECG interpretation. The magnitude of lung function impairment should be taken into account to uncover other cardiac disease and to prevent misdiagnosis.

Abstract The diagnosis of depression, a frequent comorbidity of chronic obstructive pulmonary disease (COPD), is often supported by questionnaires, such as the Patient Health Questionnaire 9 (PHQ-9). It is unknown to which extent its single questions are affected by the clinical characteristics of COPD patients. We addressed this question in 2255 GOLD grade 1–4 patients from the COSYCONET (COPD and Systemic Consequences - Comorbidities Network) COPD cohort. The dependence on COPD severity was assessed using symptoms, exacerbation risk (GOLD A-D; modified Medical Research Council dyspnoea scale (mMRC)), and frequent comorbidities as predictors of PHQ-9 results, while including age, gender, body mass index (BMI) and smoking habits as covariates. Symptoms and exacerbation risk were associated with depression in an additive manner, with mean elevations in the PHQ-9 sum score by 2.75 and 1.44 points, respectively. Asthma, sleep apnoea, gastrointestinal disorders, osteoporosis and arthritis were linked to increases by 0.8 to 1.3 points. Overall, the COPD characteristics contributed to the mean PHQ-9 score by increases from 4.5 or 5.2 to 6.3 points, respectively, when either taking GOLD A as reference or the absence of comorbidities. This finding was independent of the diagnosis of mental disorder or the intake of antidepressants. The presence of COPD led to an increase in the proportion of scores indicating depression from 12 to 22%. Single item analysis revealed homogenous effects regarding GOLD groups, but heterogeneous effects regarding GOLD grades. These findings indicate specific effects of COPD severity on the PHQ-9 depression score, especially symptoms and exacerbation risk, explaining the high prevalence of depression in COPD. Alternative explanations like an overlap of COPD severity and PHQ-9 items are discussed. Of note, we also found COPD treatment effects on depression scores.

Background Air trapping and lung hyperinflation are major determinants of prognosis and response to therapy in chronic obstructive pulmonary disease (COPD). They are often determined by body plethysmography, which has limited availability, and so the question arises as to what extent they can be estimated via spirometry. Methods We used data from visits 1–5 of the COPD cohort COSYCONET. Predictive parameters were derived from visit 1 data, while visit 2–5 data was used to assess reproducibility. Pooled data then yielded prediction models including sex, age, height, and body mass index as covariates. Hyperinflation was defined as ratio of residual volume (RV) to total lung capacity (TLC) above the upper limit of normal. (ClinicalTrials.gov identifier: NCT01245933). Results Visit 1 data from 1988 patients (Global Initiative for Chronic Obstructive Lung Disease grades 1–4, n=187, 847, 766, 188, respectively) were available for analysis (n=1231 males, 757 females; mean±sd age 65.1±8.4 years; forced expiratory volume in 1 s (FEV1) 53.1±18.4 % predicted (% pred); forced vital capacity (FVC) 78.8±18.8 % pred; RV/TLC 0.547±0.107). In total, 7157 datasets were analysed. Among measures of hyperinflation, RV/TLC showed the closest relationship to FEV1 % pred and FVC % pred, which were sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting covariates, hyperinflation was predicted by FEV1 % pred, FVC % pred or their combination with an area under the curve of 0.870, 0.864 and 0.889, respectively. Conclusions The degree of air trapping/hyperinflation in terms of RV/TLC can be estimated in a simple manner from forced spirometry, with an accuracy sufficient for inferring the presence of hyperinflation. This may be useful for clinical settings, where body plethysmography is not available.

Abstract Background There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages. Methods Sixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 (“BOS binary-early”), and stages 0/0-p/1 versus 2/3 (“BOS binary-late”) were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis. Results Regarding the recognition of “BOS binary-early”, among spirometric parameters forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding “BOS binary-late”, DLNO was inferior to bodyplethysmographic parameters. Conclusion Although the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV1, the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.

Abstract Background Recent investigations showed single associations between uric acid levels, functional parameters, exacerbations and mortality in COPD patients. The aim of this study was to describe the role of uric acid within the network of multiple relationships between function, exacerbation and comorbidities. Methods We used baseline data from the German COPD cohort COSYCONET which were evaluated by standard multiple regression analyses as well as path analysis to quantify the network of relations between parameters, particularly uric acid. Results Data from 1966 patients were analyzed. Uric acid was significantly associated with reduced FEV1, reduced 6-MWD, higher burden of exacerbations (GOLD criteria) and cardiovascular comorbidities, in addition to risk factors such as BMI and packyears. These associations remained significant after taking into account their multiple interdependences. Compared to uric acid levels the diagnosis of hyperuricemia and its medication played a minor role. Conclusion Within the limits of a cross-sectional approach, our results strongly suggest that uric acid is a biomarker of high impact in COPD and plays a genuine role for relevant outcomes such as physical capacity and exacerbations. These findings suggest that more attention should be paid to uric acid in the evaluation of COPD disease status.

Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC. In this report, we describe the case of a 34-year-old female patient of Asian origin with a post-partum initial diagnosis of pulmonary LELC. Multimodal treatment with chemoimmunotherapy and hypofractionated irradiation to the primary tumour and main metastatic sites led to a favourable response demonstrating that radiotherapy may potentially augment anti-tumour immunity. To the best of our knowledge, this is the first case report on this novel therapy strategy of multi-site hypofractionated radiotherapy and chemoimmunotherapy for metastatic pulmonary EBV-associated LELC.

Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1-4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV1) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication.