Search

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 < 0.001). In ICU patients (n = 100 transferred, n = 115 non-transferred) it was 12.0 (8.3–18.0) and 22.0 (15.0–34.0) days (p < 0.001). Beyond ECMO therapy (4.5%), reasons for transfer were medical (33.2%) or capacity (61.9%) reasons, with medical/capacity reasons in 32/49 of non-ICU and 21/74 of ICU patients. Thus, the transfer of COVID-19 patients between hospitals was associated with longer periods of hospitalization, corresponding to greater health care utilization, for which specific patient characteristics and clinical decisions played a role. [ABSTRACT FROM AUTHOR]

Background: Staff shortages pose a major challenge to the health system. Objectives: The objective of this study was to clarify the role of different causative factors we investigated on staff absenteeism during the COVID pandemic. Methods: The prospective multicentre cohort study assessed the private and professional impact of the pandemic on health care workers (HCWs) using a specially developed questionnaire. HCWs from 7 specialist lung clinics throughout Germany were surveyed from December 1 to December 23, 2021. The current analysis addresses pandemic-related absenteeism. Results: 1,134 HCW (55% female; 18.4% male, 26.3% not willing to provide information on age or gender) participated. 72.8% had received at least one vaccination dose at the time of the survey, and 9.4% reported a COVID infection. Of those with positive tests, 98% reported home quarantine for median (IQR) 14 (12–17) days; 10.3% of those who ultimately tested negative also reported quarantine periods of 14 (7–14) days. 32.2% of vaccinated respondents reported absenteeism due to vaccine reactions of 2 (1–3) days. Overall, 37% (n = 420) of HCW reported pandemic-related absenteeism, with 3,524 total days of absenteeism, of which 2,828 were due to illness/quarantine and 696 to vaccination effects. Independent risk factors for COVID-related absenteeism ≥5 days included already having COVID, but also concern about long-term effects of COVID (OR 1,782, p = 0.014); risk factors for vaccine-related absenteeism ≥2 days included concerns of late effects of vaccination (OR 2.2, 95% CI: 1.4–3.1, p < 0.000). Conclusion: Staff shortages due to quarantine or infections and vaccine reactogenicity have put a strain on German respiratory specialists. The fact that staff concerns also contributed to absenteeism may be helpful in managing future pandemic events to minimize staff absenteeism. [ABSTRACT FROM AUTHOR]

Purpose: To develop a simple score for the outcomes from COVID-19 that integrates information obtained at the time of admission including the Ct value (cycle threshold) for SARS-CoV-2. Methods: Patients with COVID-19 hospitalized from February 1st to May 31st 2021 in RoMed hospitals, Germany, were included. Clinical and laboratory parameters upon admission were recorded and patients followed until discharge or death. Logistic regression analysis was used to determine predictors of outcomes. Regression coefficients were used to develop a risk score for death. Results: Of 289 patients (46% female, median age 66 years), 29% underwent high-flow nasal oxygen (HFNO) therapy, 28% were admitted to the Intensive Care Unit (ICU, 51% put on invasive ventilation, IV), and 15% died. Age > 70 years, oxygen saturation ≤ 90%, oxygen supply upon admission, eGFR ≤ 60 ml/min and Ct value ≤ 26 were significant (p < 0.05 each) predictors for death, to which 2, 2, 1, 1 and 2 score points, respectively, could be attributed. Sum scores of ≥ 4 or ≥ 5 points were associated with a sensitivity of 95.0% or 82.5%, and a specificity of 72.5% or 81.7% regarding death. The high predictive value of the score was confirmed using data obtained between December 15th 2020 and January 31st 2021 (n = 215). Conclusion: In COVID-19 patients, a simple scoring system based on data available shortly after hospital admission including the Ct value had a high predictive value for death. The score may also be useful to estimate the likelihood for required interventions at an early stage. [ABSTRACT FROM AUTHOR]

Background: Gender differences in vaccine acceptance among health care workers (HCWs) are well documented, but the extent to which these depend on occupational group membership is less well studied. We aimed to determine vaccine acceptance and reasons of hesitancy among HCWs of respiratory clinics in Germany with respect to gender and occupational group membership. Methods: An online questionnaire for hospital staff of all professional groups was created to assess experiences with and attitudes towards COVID-19 and the available vaccines. Employees of five clinics were surveyed from 15 to 28 March 2021. Results: 962 employees (565 [72%] female) took part in the survey. Overall vaccination acceptance was 72.8%. Nurses and physicians showed greater willingness to be vaccinated than members of other professions (72.8%, 84.5%, 65.8%, respectively; p = 0.006). In multivariate analyses, worries about COVID-19 late effects (odds ratio (OR) 2.86; p < 0.001) and affiliation with physicians (OR 2.20; p = 0.025) were independently associated with the willingness for vaccination, whereas age <35 years (OR 0.61; p = 0.022) and worries about late effects of vaccination (OR 0.13; p < 0.001) predicted vaccination hesitancy; no differences were seen with respect to gender. In separate analyses for men and women, only for men worries about COVID-19 late effects were relevant, while among women, age <35 years, worries about late effects of vaccination and worries about COVID-19 late effects played a role. Conclusions: There was no overall difference in vaccination acceptance between male and female HCWs, but there were gender-specific differences in the individual reasons on which this decision-making was based. [ABSTRACT FROM AUTHOR]

Background: Oxygenated hemoglobin(OxyHem) is a simple-to-measure marker of oxygen content capable of predicting all-cause mortality in stable chronic obstructive pulmonary disease (COPD). Objectives: We aimed to analyze its predictive value during acute exacerbations of COPD (AECOPD). Methods: In this retrospective study, data from 227 patients discharged after severe AECOPD at RoMed Clinical Center Rosenheim, Germany, between January 2012 and March 2018, was analyzed. OxyHem (hemoglobin concentration [Hb] × fractional SpO2, g/dL) was calculated from oxygen saturation measured by pulse oximetry and hemoglobin assessed within 24 h after admission. The follow-up (1.7 ± 1.5 years) covered all-cause mortality, including readmissions for severe AECOPD. Results: During the follow-up period, 127 patients died, 56 due to AECOPD and 71 due to other reasons. Survivors and non-survivors showed differences in age, FVC % predicted, C-reactive protein, hemoglobin, Cr, Charlson Comorbidity Index (CCI), and OxyHem (p < 0.05 each). Significant independent predictors of survival were BMI, Cr or CCI, FEV1 % predicted or FVC % predicted, Hb, or OxyHem. The predictive value of OxyHem (p = 0.006) was superior to that of Hb or SpO2 and independent of oxygen supply during blood gas analysis. OxyHem was also predictive when using a cutoff value of 12.1 g/dL identified via receiver operating characteristic curves in analyses including either the CCI (hazard ratio 1.85; 95% CI 1.20, 2.84; p = 0.005) or Cr (2.04; 95% CI 1.35, 3.10; p = 0.001) as covariates. Conclusion: The concentration of OxyHem provides independent, easy-to-assess information on long-term mortality risk in COPD, even if measured during acute exacerbations. It therefore seems worth to be considered for broader clinical use. [ABSTRACT FROM AUTHOR]

Background: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease.Methods: Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort. The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles. The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities.Results: Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD. AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT) compared with COPD patients without AATD. There were no significant differences between groups regarding indirect costs and HRQL.Conclusion: Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD. AT was not associated with lower costs or higher HRQL.Trial Registration: NCT01245933. [ABSTRACT FROM AUTHOR]

Background: An impairment of CO diffusing capacity has been shown in diabetic patients without lung disease. We analyzed how diffusing capacity in patients with COPD is affected by the concurrent diagnosis of diabetes.Methods: Data from the initial visit of the German COPD cohort COSYCONET were used for analysis. 2575 patients with complete lung function data were included, among them 358 defined as diabetics with a reported physician diagnosis of diabetes and/or specific medication. Pairwise comparisons between groups and multivariate regression models were used to identify variables predicting the CO transfer factor (TLCO%pred) and the transfer coefficient (KCO%pred).Results: COPD patients with diabetes differed from those without diabetes regarding lung function, anthropometric, clinical and laboratory parameters. Moreover, gender was an important covariate. After correction for lung function, gender and body mass index (BMI), TLCO%pred did not significantly differ between patients with and without diabetes. The results for the transfer coefficient KCO were similar, demonstrating an important role of the confounding factors RV%pred, TLC%pred, ITGV%pred, FEV1%pred, FEV1/FVC, age, packyears, creatinine and BMI. There was not even a tendency towards lower values in diabetes.Conclusion: The analysis of data from a COPD cohort showed no significant differences of CO transport parameters between COPD patients with and without diabetes, if BMI, gender and the reduction in lung volumes were taken into account. This result is in contrast to observations in lung-healthy subjects with diabetes and raises the question which factors, among them potential anti-inflammatory effects of anti-diabetes medication are responsible for this finding. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQL) is an important patient-reported outcome measure used to describe the burden of chronic obstructive pulmonary disease (COPD) which is often accompanied by comorbid conditions.Methods: Data from 2275 participants in the COPD cohort COSYCONET and from 4505 lung-healthy control subjects from the population-based KORA and SHIP studies were pooled. Main outcomes were the five dimensions of the generic EQ-5D-3 L questionnaire and two EQ-5D index scores using a tariff based on valuations from the general population and an experience-based tariff. The association of COPD in GOLD grades 1-4 and of several comorbid conditions with the EQ-5D index scores was quantified by multiple linear regression models while adjusting for age, sex, education, body mass index (BMI), and smoking status.Results: For all dimensions of the EQ-5D, the proportion of participants reporting problems was higher in the COPD group than in control subjects. COPD was associated with significant reductions in the EQ-5D index scores (-0.05 points for COPD grades 1/2, -0.09 for COPD grade 3, -0.18 for COPD grade 4 according to the preference-based utility tariff, all p < 0.0001). Adjusted mean index scores were 0.89 in control subjects and 0.85, 0.84, 0.81, and 0.72 in COPD grades 1-4 according to the preference-based utility tariff and 0.76, 0.71, 0.68, 0.64, and 0.58 for control subjects and COPD grades 1-4 for the experience-based tariff respectively. Comorbidities had additive negative effects on the index scores; the effect sizes for comorbidities were comparable to or smaller than the effects of COPD grade 3. No statistically significant interactions between COPD and comorbidities were observed. Score differences between COPD patients and control subjects were most pronounced in younger age groups.Conclusions: Compared with control subjects, the considerable reduction of HRQL in patients with COPD was mainly due to respiratory limitations, but observed comorbidities added linearly to this effect. Younger COPD patients showed a greater loss of HRQL and may therefore be in specific need of comprehensive disease management.Trial Registration: NCT01245933. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient's health-related quality of life (HRQL). While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health. This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George's Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.Methods: Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions. Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.Results: In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease. Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions. The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions. For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.Conclusion: All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities. Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models. [ABSTRACT FROM AUTHOR]

Background: The diagnostic use of lung function using spirometry depends on the validity of reference equations. A multitude of spirometric prediction values have been published, but in most of these studies older age groups are underrepresented. Objectives: The aim of the present study was to establish new spirometric reference values for advanced age and to compare these to recent prediction equations from population-based studies. Methods: In the present study spirometry was performed in a population-based sample from the KORA-F4 and KORA-Age cohorts (2006-2009, Augsburg, Germany) comprising 592 never-smoking subjects aged 42-89 years and with no history of respiratory disease. Using quantile regression analysis, equations for the median and lower limit of normal were derived for indices characterizing the expiratory flow-volume curve: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF25, FEF50 and FEF75). Results: FEV1 and FVC were slightly higher, and PEF was lower compared to recently published equations. Importantly, forced expiratory flow rates at middle and low lung volume, as putative indicators of small airway disease, were in good agreement with recent data, especially for older age. Conclusion: Our study provides up-to-date reference equations for all major indices of flow-volume curves in middle and advanced age in a South German population. The small deviations from published equations indicate that there might be some regional differences of lung function within the Caucasian population of advanced age in Europe. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: For percutaneously tracheostomized patients with prolonged weaning and persisting respiratory failure, the adequate time point for safe decannulation and switch to noninvasive ventilation is an important clinical issue. Objectives: We aimed to evaluate the usefulness of a tracheostomy retainer (TR) and the predictors of successful decannulation. Methods: We studied 166 of 384 patients with prolonged weaning in whom a TR was inserted into a tracheostoma. Patients were analyzed with regard to successful decannulation and characterized by blood gas values, the duration of previous spontaneous breathing, Simplified Acute Physiology Score (SAPS) and laboratory parameters. Results: In 47 patients (28.3%) recannulation was necessary, mostly due to respiratory decompensation and aspiration. Overall, 80.6% of the patients could be liberated from a tracheostomy with the help of a TR. The need for recannulation was associated with a shorter duration of spontaneous breathing within the last 24/48 h (p < 0.01 each), lower arterial oxygen tension (p = 0.025), greater age (p = 0.025), and a higher creatinine level (p = 0.003) and SAPS (p < 0.001). The risk for recannulation was 9.5% when patients breathed spontaneously for 19-24 h within the 24 h prior to decannulation, but 75.0% when patients breathed for only 0-6 h without ventilatory support (p < 0.001). According to ROC analysis, the SAPS best predicted successful decannulation [AUC 0.725 (95% CI: 0.634-0.815), p < 0.001]. Recannulated patients had longer durations of intubation (p = 0.046), tracheostomy (p = 0.003) and hospital stay (p < 0.001). Conclusion: In percutaneously tracheostomized patients with prolonged weaning, the use of a TR seems to facilitate and improve the weaning process considerably. The duration of spontaneous breathing prior to decannulation, age and oxygenation describe the risk for recannulation in these patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods: Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland- Altman plots were established to evaluate the agreement between predicted and measured values. Results: The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. Conclusions: Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient. [ABSTRACT FROM AUTHOR]

This study aimed to identify predictive (bio-)markers for COVID-19 severity derived from automated quantitative thin slice low dose volumetric CT analysis, clinical chemistry and lung function testing. Seventy-four COVID-19 patients admitted between March 16th and June 3rd 2020 to the Asklepios Lung Clinic Munich-Gauting, Germany, were included in the study. Patients were categorized in a non-severe group including patients hospitalized on general wards only and in a severe group including patients requiring intensive care treatment. Fully automated quantification of CT scans was performed via IMBIO CT Lung Texture analysis™ software. Predictive biomarkers were assessed with receiver-operator-curve and likelihood analysis. Fifty-five patients (44% female) presented with non-severe COVID-19 and 19 patients (32% female) with severe disease. Five fatalities were reported in the severe group. Accurate automated CT analysis was possible with 61 CTs (82%). Disease severity was linked to lower residual normal lung (72.5% vs 87%, p = 0.003), increased ground glass opacities (GGO) (8% vs 5%, p = 0.031) and increased reticular pattern (8% vs 2%, p = 0.025). Disease severity was associated with advanced age (76 vs 59 years, p = 0.001) and elevated serum C-reactive protein (CRP, 92.2 vs 36.3 mg/L, p < 0.001), lactate dehydrogenase (LDH, 485 vs 268 IU/L, p < 0.001) and oxygen supplementation (p < 0.001) upon admission. Predictive risk factors for the development of severe COVID-19 were oxygen supplementation, LDH >313 IU/L, CRP >71 mg/L, <70% normal lung texture, >12.5% GGO and >4.5% reticular pattern. Automated low dose CT analysis upon admission might be a useful tool to predict COVID-19 severity in patients. • Automated quantitative thin slice volumetric low dose CT analysis could be a useful tool for prediction of COVID-19 severity on admission. • Need for oxygen supplementation, LDH >313 IU/L and CRP >71 mg/L were identified as clinical markers predicting disease severity. • Normal lung texture <70%, GGO >12.5% and reticular pattern >4.5% in CT were indicative of severe disease. [ABSTRACT FROM AUTHOR]

Background: The 2017 ATS/ERS technical standard for measuring the single-breath diffusing capacity (DLCO) proposed the "rapid-gas-analyzer" (RGA) or, equivalently, "total-breath" (TB) method for the determination of total lung capacity (TLC). In this study, we compared DLCO and TLC values estimated using the TB and conventional method, and how estimated TLC using these two methods compared to that determined by body plethysmography., Method: A total of 95 people with COPD (GOLD grades 1-4) and 23 healthy subjects were studied using the EasyOne Pro (ndd Medical Technologies, Switzerland) and Master Screen Body (Vyaire Medical, Höchberg, Germany)., Results: On average the TB method resulted in higher values of DLCO (mean ± SD Δ = 0.469 ± 0.267; 95%CI: 0.420; 0.517 mmol*min-1*kPa-1) and TLC (Δ = 0.495 ± 0.371; 95%CI: 0.427; 0.562 L) compared with the conventional method. In healthy subjects the ratio between TB and conventional DLCO was close to one. TLC estimated using both methods was lower than that determined by plethysmography. The difference was smaller for the TB method (Δ = 1.064 ± 0.740; 95%CI: 0.929; 1.199 L) compared with the conventional method (Δ = 1.558 ± 0.940; 95%CI: 1.387; 1.739 L). TLC from body plethysmography could be estimated as a function of TB TLC and FEV 1 Z-Score with an accuracy (normalized root mean square difference) of 9.1%., Conclusion: The total-breath method yielded higher values of DLCO and TLC than the conventional analysis, especially in subjects with COPD. TLC from the total-breath method can also be used to estimate plethysmographic TLC with better accuracy than the conventional method. The study is registered under clinicaltrial.gov NCT04531293., (© 2024. The Author(s).)

Background: In hospitalized patients with SARS-CoV-2 infection, outcomes markedly differ between locations, regions and countries. One possible cause for these variations in outcomes could be differences in patient treatment limitations (PTL) in different locations. We thus studied their role as predictor for mortality in a population of hospitalized patients with COVID-19., Methods: In a region with high incidence of SARS-CoV-2 infection, adult hospitalized patients with PCR-confirmed SARS-CoV-2 infection were prospectively registered and characterized regarding sex, age, vital signs, symptoms, comorbidities (including Charlson comorbidity index (CCI)), transcutaneous pulse oximetry (SpO 2 ) and laboratory values upon admission, as well as ICU-stay including respiratory support, discharge, transfer to another hospital and death. PTL assessed by routine clinical procedures comprised the acceptance of ICU-therapy, orotracheal intubation and/or cardiopulmonary resuscitation., Results: Among 526 patients included (median [quartiles] age 73 [57; 82] years, 47% female), 226 (43%) had at least one treatment limitation. Each limitation was associated with age, dementia and eGFR (p < 0.05 each), that regarding resuscitation additionally with Charlson comorbidity index (CCI) and cardiac disease. Overall mortality was 27% and lower (p < 0.001) in patients without treatment limitation (12%) compared to those with any limitation (47%). In univariate analyses, age and comorbidities (diabetes, cardiac, cerebrovascular, renal, hepatic, malignant disease, dementia), SpO 2 , hemoglobin, leucocyte numbers, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), Interleukin-6 and LDH were predictive for death (p < 0.05 each). In multivariate analyses, the presence of any treatment limitation was an independent predictor of death (OR 4.34, 95%-CI 2.10-12.30; p = 0.001), in addition to CCI, eGFR < 55 ml/min, neutrophil number > 5 G/l, CRP > 7 mg/l and SpO 2  < 93% (p < 0.05 each)., Conclusion: In hospitalized patients with SARS-CoV-2, the percentage of patients with treatment limitations was high. PTL were linked to age, comorbidities and eGFR assessed upon admission and strong, independent risk factors for mortality. These findings might be useful for further understanding of COVID-19 mortality and its regional variations. Clinical trial registration ClinicalTrials.gov Identifier: NCT04344171.

Introduction: The measurement of fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and might substitute for bronchial provocation (BP) tests. To evaluate the diagnostic accuracy of FeNO within a confirmatory study, the following hypotheses will be tested: (1) A FeNO cut-off >50 ppb (parts per billion) is suitable for diagnosing asthma (sensitivity 35%, specificity 95%); (2) If the clinical symptoms 'allergic rhinitis' and 'wheezing' are present, asthma can be diagnosed at FeNO >33 ppb with a positive predictive value (PPV) > 70% and (3) A FeNO >33 ppb can predict responsiveness to inhaled corticosteroid (ICS) with a PPV > 70%., Methods and Analysis: A prospective diagnostic study will be conducted in three practices of pneumologists in Germany. 300 patients suspected of suffering from asthma will be included. As an index test, patients perform FeNO measurement with the device NIOX VERO. As reference a test, patients are examined with whole bodyplethysmography and BP, if necessary. After 3 months, patients with an asthma diagnosis will be examined again to verify the diagnosis and evaluate ICS responsiveness. Patients who did not receive an asthma diagnosis at the initial examination will be phoned after 3 months and asked about persistent respiratory symptoms to exclude false negative findings. As a primary target, sensitivity and specificity of FeNO >50 ppb will be determined. As a secondary target the PPV for asthma at FeNO >33 ppb, when the symptoms 'allergic rhinitis' and 'wheezing' are present, will be calculated. Regarding ICS responsiveness, the PPV of FeNO >33 ppb will be determined., Ethics and Dissemination: The study was approved by the Ethical Committee of the Technical University of Munich (Reference number 122/20 S). The major results will be published in peer-reviewed academic journals and disseminated through conferences., Trial Registration Number: DRKS00021125., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis., Study Design and Setting: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV 1 ) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV 1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression., Results: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P < 0.001) and sensitivities (not significant) when evaluated with WBP; also, Youden indices increased in these CSS (P < 0.05). AUC of FeNO in combination with 'wheezing' and 'allergic rhinitis' when WBP was used as RS (AUC = 0.724; 95% confidence interval 0.672 to 0.776) was higher compared with spirometry as RS (AUC = 0.654; 95% confidence interval 0.585 to 0.722) (P < 0.001)., Conclusion: In case of asthma, superior RS led to more favorable assessment of index tests. FeNO measurement might have been underestimated in some previous studies., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with COPD-specific symptoms and history but FEV1/FVC ratio ≥0.7 are a heterogeneous group (former GOLD grade 0) with uncertainties regarding natural history., Objective: We investigated which lung function measures and cutoff values are predictive for deterioration according to GOLD grades and all-cause mortality., Methods: We used visit 1-4 data of the COSYCONET cohort. Logistic and Cox regression analyses were used to identify relevant parameters. GOLD 0 patients were categorized according to whether they maintained grade 0 over the following 2 visits or deteriorated persistently into grades 1 or 2. Their clinical characteristics were compared with those of GOLD 1 and 2 patients., Results: Among 2,741 patients, 374 GOLD 0, 206 grade 1, and 962 grade 2 patients were identified. GOLD 0 patients were characterized by high symptom burden, comparable to grade 2, and a restrictive lung function pattern; those with FEV1/FVC above 0.75 were unlikely to deteriorate over time into grades 1 and 2, in contrast to those with values between 0.70 and 0.75. Regarding mortality risk in GOLD 0, FEV1%predicted and age were the relevant determinants, whereby a cutoff value of 65% was superior to that of 80% as proposed previously., Conclusions: Regarding patients of the former GOLD grade 0, we identified simple criteria for FEV1/FVC and FEV1% predicted that were relevant for the outcome in terms of deterioration over time and mortality. These criteria might help to identify patients with the typical risk profile of COPD among those not fulfilling spirometric COPD criteria., (© 2021 S. Karger AG, Basel.)

High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00-1.87) compared to baseline RHR ≤ 72 bpm. The time-updated RHR > 72 bpm was markedly superior (HR 1.79, 1.30-2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.

Background: In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET., Material and Methods: Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history., Results: Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all p <0.05)., Conclusions: Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time., Competing Interests: Johanna I Lutter reports grants from German Federal Ministry of Education and Research during the conduct of the study. Stefan Karrasch reports grants from German Federal Ministry of Education and Research (BMBF) during the conduct of the study. Holger Schulz report grants from German Federal Ministry of Education and Research (BMBF), during the conduct of the study. Claus Vogelmeier report grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from CSL Behring, personal fees from Chiesi, grants and personal fees from GlaxoSmithKline, grants and personal fees from Grifols, personal fees from Menarini, personal fees from Mundipharma, grants and personal fees from Novartis, personal fees from Teva, personal fees from Cipla, grants from Bayer Schering Pharma AG, grants from MSD, and grants from Pfizer outside the submitted work. Rolf Holle report grants from German Federal Ministry of Education and Research, during the conduct of the study. The authors report no other conflicts of interest in this work.

Background: Chronic obstructive pulmonary disease (COPD) is common around the world and carries a high morbidity and mortality. Symptom- and risk-oriented drug treatment is recommended, both in Germany and in other countries. It is not yet known to what extent the treatment that is actually delivered in Germany corresponds to the current recommendations in the guidelines., Methods: As recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2017, 2281 patients of the national COPD cohort COSYCONET (COPD and Systemic Consequences-Comorbidities Network) were classified into Gold classes A-D on the basis of disease-specific manifestations and the frequency of exacerbations. Moreover, the regular use of medications was documented and categorized according to active substance groups. For all groups, the documented treatment that was actually given was compared to the recommended treatment., Results: 67.6% of the patients received a combination of a long-acting anticholinergic drug (LAMA) and a long-acting beta-mimetic drug (LABA), while 65.8% received inhaled corticosteroids (ICS), 11.7% theophylline, and 12.6% oral corticosteroids (OCS). Despite recommendations to the contrary, 66% of the patients in Groups A and B (low exacerbation rates) were treated with ICS; some of these patients carried an additional diagnosis of bronchial asthma. There was evidence of undertreatment mainly in groups C and D (high exacerbation rate), because many of the patients in these groups were not treated with LAMA or LAMA/LABA as recommended., Conclusion: The observed deviations from the recommended treatment, some of which were substantial, might lead to suboptimal treatment outcomes as well as to avoidable side effects of medication.

Patients with COPD are often of advanced age and have a high number of medications due to their lung disease and comorbidities. Thus they are at risk for unwanted effects from drugs, either due to age or due to interactions between drugs. These issues are not clarified. We therefore assessed the number of medications and potential adverse effects in a large cohort of patients with COPD. The analysis was performed in 2741 patients of the German COPD cohort COSYCONET, using baseline data (visit 1) and follow-up data after about 1.5 years (visit 3). Spirometric GOLD grades 1-4 were found in 8/35/32/9% of patients and GOLD groups ABCD in 7/25/4/48% of patients, while the remaining patients (n = 450, 16.4%) could not be classified according to GOLD criteria. The compatibility of medication with age was evaluated via the PRISCUS list, drug interactions via the AiD clinic system, whereby only drug combinations occurring in at least 10 patients were considered (nine unwanted interactions, one wanted interaction). The median numbers of medications were 5 or more in all patient categories, among them 3 or more non-respiratory medications. In the total population there were 153 patients (10.2%) aged ≥65 years who had any medication of the PRISCUS list with intermediate or low risk. Serious adverse combinations of drugs according to AiD occurred in 114 patients (4.2%), while the number of unwanted but only potentially clinically relevant combinations was 175 (6.4%). The number of wanted combinations was 219 (8.0%). These numbers did not markedly change when restricting the analysis to patients of GOLD grades 1-4. Moreover, the results were similar for visit 1 and visit 3. We conclude that in a large cohort of COPD patients about 10% of patients aged at least 65 years had medications that could interfere with their age and that the proportions of patients with either unwanted or wanted drug interactions were both in the range of 8-10%. These results suggest that problems arising from the high number of medications were not very frequent in the COPD cohort analysed., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: To evaluate the influence of the practice setting on diagnostic accuracy of fractional exhaled nitric oxide (FENO) for diagnosing asthma; and to develop prediction rules for diagnostic decision-making including clinical signs and symptoms (CSS)., Setting: Patients from 10 general practices and 1 private practice of 5 pneumologists in ambulatory care., Participants: 553 patients, 57.9% female. Consecutive inclusion of diagnostic-naive patients suspected of suffering from obstructive airway disease. Exclusion criteria were respiratory tract infections within the last 6 weeks., Interventions: The index test was FENO measurement. Reference standard was the Tiffeneau ratio (forced expiratory volume in 1 s/vital capacity) or airway resistance as assessed by whole body plethysmography, with additional bronchoprovocation or bronchodilator testing., Primary and Secondary Outcome Measures: Asthma as determined by pneumologists, who were blind to FENO measurement results. Prediction rules were derived from multiple logistic regression analysis. A freely available calculator that allows computing all combinations was developed., Results: The practice setting only had minor influence on sensitivities of FENO cut-off points. In the final model (n=472), allergic rhinitis, wheezing and previous medication were positively associated with asthma. Increasing age and recurrent respiratory tract infections were negatively associated. The area under the curve (AUC) of FENO (AUC=0.650; 95% CI 0.599 to 0.701) increased significantly (p<0.0001) when combined with CSS (AUC=0.753; 95% CI 0.707 to 0.798). Presence of wheezing and allergic rhinitis allowed ruling in asthma with FENO >30 ppb. Ruling out with FENO <16 ppb in patients <43 years was only possible without allergic symptoms when recurrent respiratory tract infections were present., Conclusions: FENO results should be interpreted in the context of CSS to enhance their diagnostic value in primary care. The final diagnostic model appears as a sound algorithm fitting well to the established diagnostic rules related to CSS of asthma. FENO appears more effective for ruling in asthma than for ruling it out., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: In patients with COPD, chronic anemia is known as an unfavorable prognostic factor. Whether the association between hemoglobin (Hb) levels and long-term survival is restricted to anemia or extends to higher Hb levels has not yet been systematically assessed., Methods: We determined Hb levels in 309 subjects with COPD and chronic respiratory failure prior to initiation of noninvasive ventilation, accounting for confounders that might affect Hb. Subjects were categorized as anemic (Hb < 12 g/dL in females, Hb < 13 g/dL in males), polycythemic (Hb ≥ 15 g/dL in females, Hb ≥ 17 g/dL in males), or normocythemic. In addition, percentiles of Hb values were analyzed with regard to mortality from any cause., Results: Two-hundred seven subjects (67.0%) showed normal Hb levels, 46 (14.9%) had anemia, and 56 (18.1%) had polycythemia. Polycythemic subjects showed a higher survival rate than anemic (P = .01) and normocythemic subjects (P = .043). In a univariate Cox hazards model, Hb was associated with long-term survival (hazard ratio 0.855; 95% CI 0.783-0.934, P < .001). The 58th percentiles of Hb (14.3 g/dL in females, 15.1 g/dL in males) yielded the highest discriminative value for predicting survival (hazard ratio 0.463, 95% CI 0.324-0.660, P < .001). In the multivariate analysis this cutoff was an independent predictor for survival (hazard ratio 0.627, 95% CI 0.414-0.949, P = .03), in addition to age and body mass index., Conclusions: In subjects with COPD and chronic respiratory failure undergoing treatment with noninvasive ventilation and LTOT, high Hb levels are associated with better long-term survival. The optimal cutoff level for prediction was above the established threshold defining anemia. Thus, predicting survival only on the basis of anemia does not fully utilize the prognostic potential of Hb values in COPD.

The aim of the current study was to determine the impact and interaction of important influencing factors on the fraction of exhaled nitric oxide (FeNO). FeNO was measured in a population-based sample of 1250 middle-aged subjects from the KORA F4 cohort (Augsburg, Germany). Analysis of covariance models was performed including the factors age, height, FVC, FEV(1), sex, current smoking status, recent respiratory tract infection, and respiratory allergy. Geometric mean (SD as factor; 95% confidence interval as factor) FeNO was 13.9 (1.9; 1.033) ppb. FeNO significantly depended on age, height, smoking, infection and allergy. Smoking reduced FeNO by 21%, while infection and allergy led to increases by 9 and 11%, respectively. Increases in age by 10 years and in height by 10 cm were associated with increases of FeNO by 15 and 10%, respectively. Non-smokers demonstrated independent multiplicative superposition of factors affecting FeNO while the effect of allergy was virtually eliminated in smokers without infection. We conclude that in middle-aged non-smokers the effects of infection, age and height can be easily taken into account and do not significantly disturb the effect of respiratory tract allergies on FeNO. In current smokers, however, effects were heterogeneous and information on smoking intensity seems to be useful for better adjustment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases worldwide, and its morbidity and mortality are still increasing. Thus, it is expected that, globally, COPD will be the third most common cause of death by 2020. Moreover, COPD leads to enormous health-economic costs (i. e., outpatient and inpatient treatment, inability to work). Nevertheless, the prevalence of COPD is underestimated also in Germany. This is partly because often, the disease is symptomatic only in its advanced stages and as a result it is not diagnosed until late. In addition, the therapeutic effects on the long-term course and the progression of the disease are limited. Therefore, a much deeper understanding of the manifold and complex pathomechanisms of this pathomorphologically varied disease is needed before new therapeutic strategies can be developed. The aim of this review is to discuss current concepts of the pathophysiology of COPD and their scientific bases. The authors will concentrate mainly on a differentiated description of the pathomechanisms which cause chronic obstructive bronchiolitis and obstructive pulmonary emphysema.

Objective: The effects of passive smoke exposure on respiratory health are still under debate. Therefore, we examined the risk of respiratory symptoms related to passive smoke exposure among German adults within the European Community Respiratory Health Survey., Methods: The questionnaire data of the population-based sample (n = 1,890) were analyzed. Multiple logistic regression models were carried out for current asthma (asthma symptoms or medication), chronic bronchitis (cough with phlegm for > or = 3 months per year), and wheezing as dependent variables, and self-reported exposure to passive smoke at home and at the workplace as independent variables after adjusting for city, age, gender, active smoking, and socioeconomic status as well as occupational exposure to dusts and/or gases., Results: The relative odds for chronic bronchitis were significantly higher in subjects reporting involuntary tobacco smoke exposure in the workplace (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.16 to 3.11). Likewise, the adjusted OR for asthma was slightly elevated (OR, 1.51; 95% CI, 0.99 to 2.32). The risk of chronic bronchitis (OR, 3.07; 95% CI, 1.56 to 6.06), asthma (OR, 2.06; 95% CI, 1.07 to 3.97), and wheezing (OR, 2.12; 95% CI, 1.25 to 3.58) increased significantly with a daily exposure of > 8 h., Conclusion: The control of passive smoke exposure in the workplace might reduce the risk of respiratory symptoms independently of exposure to other airborne contaminants.