The total-breath method yields higher values of DLCO and TLC than the conventional method.

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 FEV1 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.

Effects of triple therapy on disease burden in patients of GOLD groups C and D: results from the observational COPD cohort COSYCONET.

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 < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed. CONCLUSION: Without statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds.

Implications of Switching from Conventional to Electronic Cigarettes on Quality of Life and Smoking Behaviour: Results from the EQualLife Trial.

INTRODUCTION: Electronic cigarettes and "vaping" have become popular since their appearance in Europe and the USA in approximately 2006. They are often perceived as having fewer health risks than conventional cigarettes, which makes them of interest as a support tool in smoking cessation. However, its efficacy regarding cessation or reduction of smoking under real-life conditions remains controversial. Our objective was to clarify this question in an observational study of smoking habits after initiating vaping without targeted intervention, as compared to a validated cessation programme. METHODS: From October 2015 to April 2018, 80 subjects (60 in the e-cigarette group and 20 in the supervised smoking cessation group) were included in two trial visits, one at the start of the trial and the second after 3 months, plus 4 questionnaire surveys: at the start of the trial and after a 1, 2, and 3 month period. The questionnaire included a nicotine use inventory, a modified Fagerström test for nicotine dependence, and the WHO-QOL-BREF survey. RESULTS: E-cigarettes were effective, leading to a significant (p < 0.03) reduction (p < 0.03) in tobacco consumption and nicotine dependence, with an abstinence rate of 43% after 3 months. Compared to participants in the smoking cessation programme, their use was not associated with an improvement in quality of life during the quitting attempt, and there were no significant differences in clinical symptoms between groups. The reduction in nicotine dependence was more pronounced (p < 0.012) for the smoking cessation programme, with higher abstinence rates (p = 0.011 after 12 weeks) and lower (p < 0.003) remaining tobacco consumption compared to electronic cigarettes. DISCUSSION/CONCLUSIONS: The use of electronic cigarettes reduced nicotine dependence and tobacco consumption, but a supervised smoking cessation programme was superior in terms of achieved cessation in both regards. Electronic cigarettes did not improve the quality of life. Since e-cigarettes could be associated with long-term health risks, their usefulness in smoking cessation remains questionable, and a professionally guided and validated smoking cessation programme still appears to be superior and preferable, in terms of achieved cessation. Although this trial is limited regarding the number of participants and follow-up time, it highlights the need for additional, large clinical trials evaluating the efficacy of e-cigarettes for smoking cessation in comparison to a professionally guided smoking cessation programme.

Cumulative occupational exposure to gases and fumes is associated with impairment in lung function and disease-related quality of life in a German COPD patient cohort.

OBJECTIVES: The impact of occupational exposures on lung function impairments and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) was analysed and compared with that of smoking. METHODS: Data from 1283 men and 759 women (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 or former grade 0, without alpha-1-antitrypsin deficiency) of the COPD and Systemic Consequences Comorbidities Network cohort were analysed. Cumulative exposure to gases/fumes, biological dust, mineral dust or the combination vapours/gases/dusts/fumes was assessed using the ALOHA job exposure matrix. The effect of both occupational and smoking exposure on lung function and disease-specific QoL (St George's Respiratory Questionnaire) was analysed using linear regression analysis adjusting for age, body mass index, diabetes, hypertension and coronary artery disease, stratified by sex. RESULTS: In men, exposure to gases/fumes showed the strongest effects among occupational exposures, being significantly associated with all lung function parameters and QoL; the effects were partially stronger than of smoking. Smoking had a larger effect than occupational exposure on lung diffusing capacity (transfer factor for carbon monoxide) but not on air trapping (residual volume/total lung capacity). In women, occupational exposures were not significantly associated with QoL or lung function, while the relationships between lung function parameters and smoking were comparable to men. CONCLUSIONS: In patients with COPD, cumulative occupational exposure, particularly to gases/fumes, showed effects on airway obstruction, air trapping, gas uptake capacity and disease-related QoL, some of which were larger than those of smoking. These findings suggest that lung air trapping and QoL should be considered as outcomes of occupational exposure to gases and fumes in patients with COPD. TRIAL REGISTRATION NUMBER: NCT01245933.

Causes and Risk Factors for Absenteeism among Medical Staff in German Specialized Lung Clinics during the COVID Pandemic.

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.

Preoperative risk factors predict perioperative allogenic blood transfusion in patients undergoing primary lung cancer resections: a retrospective cohort study from a high-volume thoracic surgery center.

BACKGROUND: Our study aimed to identify preoperative predictors for perioperative allogenic blood transfusion (ABT) in patients undergoing major lung cancer resections in order to improve the perioperative management of patients at risk for ABT. METHODS: Patients admitted between 2014 and 2016 in a high-volume thoracic surgery clinic were retrospectively evaluated in a cohort study based on a control group without ABT and the ABT group requiring packed red blood cell units within 15 days postoperatively until discharge. The association of ABT with clinically established parameters (sex, preoperative anemia, liver and coagulation function, blood groups, multilobar resections) was analyzed by contingency tables, receiver operating characteristics (ROC) and logistic regression analysis, taking into account potential covariates. RESULTS: 60 out of 529 patients (11.3%) required ABT. N1 and non-T1 tumors, thoracotomy approach, multilobar resections, thoracic wall resections and Rhesus negativity were more frequent in the ABT group. In multivariable analyses, female sex, preoperative anemia, multilobar resections, as well as serum alanine-aminotransferase levels, thrombocyte counts and Rhesus negativity were identified as independent predictors of ABT, being associated with OR (95% Confidence interval, p-value) of 2.44 (1.23-4.88, p = 0.0112), 18.16 (8.73-37.78, p < 0.0001), 5.79 (2.50-13.38, p < 0.0001), 3.98 (1.73-9.16, p = 0.0012), 2.04 (1.04-4.02, p = 0.0390) and 2.84 (1.23-6.59, p = 0.0150), respectively. CONCLUSIONS: In patients undergoing major lung cancer resections, multiple independent risk factors for perioperative ABT apart from preoperative anemia and multilobar resections were identified. Assessment of these predictors might help to identify high risk patients preoperatively and to improve the strategies that reduce perioperative ABT.

IgE is associated with exacerbations and lung function decline in COPD.

BACKGROUND: Both allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts. METHODS: COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD. RESULTS: Both in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12-2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32-3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy). CONCLUSION: These data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.

Quantification of pulmonary perfusion abnormalities using DCE-MRI in COPD: comparison with quantitative CT and pulmonary function.

OBJECTIVES: Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI. METHODS: We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the "COSYCONET" COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu's method, k-means clustering, texture analysis, and 80th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRMEmph) and functional small airway disease (PRMfSAD), and FEV1/FVC from PFT. RESULTS: All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p < 0.001), with the highest association based on Otsu's method (r = 0.72, p < 0.001). QDP correlated significantly with all PRM indices (p < 0.001), with the strongest correlations with PRMEmph (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRMEmph (mean difference = 35.85 to 40.40) and PRMfSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = - 0.54 to - 0.41, p < 0.001). CONCLUSION: QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRMEmph and PRMfSAD. We propose to use QDP based on Otsu's method for future clinical studies in COPD. KEY POINTS: • QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT. • The extent of QDP from DCE-MRI corresponds to the combined extent of PRMEmph and PRMfSAD from CT. • Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

A simple risk score for mortality including the PCR Ct value upon admission in patients hospitalized due to COVID-19.

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.

Effect of experimental exposures to 3-D printer emissions on nasal allergen responses and lung diffusing capacity for inhaled carbon monoxide/nitric oxide in subjects with seasonal allergic rhinitis.

3-D printers are widely used. Based on previous findings, we hypothesized that their emissions could enhance allergen responsiveness and reduce lung diffusing capacity. Using a cross-over design, 28 young subjects with seasonal allergic rhinitis were exposed to 3-D printer emissions, either from polylactic acid (PLA) or from acrylonitrile butadiene styrene copolymer (ABS), for 2 h each. Ninety minutes later, nasal allergen challenges were performed, with secretions sampled after 1.5 h. Besides nasal functional and inflammatory responses, assessments included diffusing capacity. There was also an inclusion day without exposure. The exposures elicited slight reductions in lung diffusing capacity for inhaled nitric oxide (DLNO ) that were similar for PLA and ABS. Rhinomanometry showed the same allergen responses after both exposures. In nasal secretions, concentrations of interleukin 6 and tumor necrosis factor were slightly reduced after ABS exposure versus inclusion day, while that of interleukin 5 was slightly increased after PLA exposure versus inclusion.

Oxygenated Hemoglobin Predicts Outcome in Patients with Chronic Lung Allograft Dysfunction.

BACKGROUND: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information. OBJECTIVE: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD. METHODS: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves. RESULTS: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk. CONCLUSION: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further.

Gender Differences in Health Care Workers' Risk-Benefit Trade-Offs for COVID-19 Vaccination.

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.

Patients' treatment limitations as predictive factor for mortality in COVID-19: results from hospitalized patients of a hotspot region for SARS-CoV-2 infections.

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 (SpO2) 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), SpO2, 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 SpO2 < 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.

Prediction of lung emphysema in COPD by spirometry and clinical symptoms: results from COSYCONET.

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 .

Echo Time-Dependent Observed Lung T1 in Patients With Chronic Obstructive Pulmonary Disease in Correlation With Quantitative Imaging and Clinical Indices.

BACKGROUND: There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T1 (T1 (TE)) depends on the echo-time (TE) and reflects regional pulmonary function. PURPOSE: To investigate the potential diagnostic value of T1 (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT. STUDY TYPE: Prospective non-randomized diagnostic study. POPULATION: Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference. FIELD STRENGTH/SEQUENCE: Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T1 (TE) mapping at TE1-5  = 70 µsec, 500 µsec, 1200 µsec, 1650 µsec, and 2300 µsec. ASSESSMENT: Perfusion images were scored by three radiologists. T1 (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired. STATISTICAL TESTS: Spearman rank correlation coefficients (ρ) were calculated between T1 (TE) and perfusion scores, clinical parameters and qCT. A P-value <0.05 was considered statistically significant. RESULTS: Median values were T1 (TE1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T1 was observed from TE1 to TE2 , with no changes from TE2 to TE3 (P = 0.48), TE3 to TE4 (P = 0.94) or TE4 to TE5 (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman's correlations between T1 and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ < 0.70), mean lung density (MLD, ρ < 0.72) and the perfusion score (ρ > -0.69) were found. Overall, correlations were strongest at TE2 , weaker at TE1 and rarely significant at TE4 -TE5 . DATA CONCLUSION: In COPD patients, the increase of T1 (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T1 and clinical parameters of disease at longer TEs, this suggests that T1 (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T1 (TE) mapping might be developed further to provide diagnostic information beyond T1 at a single TE. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Prognostic Value of Oxygenated Hemoglobin Assessed during Acute Exacerbations of Chronic Pulmonary Disease.

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.

Deterioration and Mortality Risk of COPD Patients Not Fitting into Standard GOLD Categories: Results of the COSYCONET Cohort.

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.

High-sensitivity troponin I and all-cause mortality in patients with stable COPD: an analysis of the COSYCONET study.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death with a considerable part of the population dying from cardiovascular diseases. High-sensitivity troponin I (hs-TnI) might help to better identify COPD patients at high risk of mortality. We aimed to study the predictive value of hs-TnI for all-cause mortality beyond established COPD assessments, and after consideration of relevant cardiovascular risk factors and prevalent cardiovascular diseases, in a broad population with stable COPD.Circulating hs-TnI concentrations together with a wide range of respiratory and cardiovascular markers were evaluated in 2085 patients with stable COPD across all severity stages enrolled in the multicentre COSYCONET cohort study. The primary outcome was all-cause mortality over 3 years of follow-up.Hs-TnI was detectable in 2020 (96.9%) patients. The median hs-TnI concentration was 3.8 ng·L-1 (interquartile range 2.5-6.6 ng·L-1), with levels above the 99th percentile reference limit of 27 ng·L-1 observed in 1.8% of patients. In Cox regression analyses including adjustments for airflow limitation, dyspnoea grade, exercise capacity and history of severe exacerbations, as well as traditional cardiovascular risk factors, estimated glomerular filtration rate, ankle-brachial index, N-terminal pro-brain natriuretic peptides and prevalent cardiovascular diseases, hs-TnI was a significant predictor for all-cause mortality, both as a continuous variable (hazard ratio (HR) for log hs-TnI 1.28, 95% CI 1.01-1.62) and categorised according to the cut-off of 6 ng·L-1 (HR 1.63, 95% CI 1.10-2.42).In patients with stable COPD, hs-TnI is a strong predictor of all-cause mortality beyond established COPD mortality predictors, and independent of a broad range of cardiovascular risk factors and prevalent cardiovascular diseases. Hs-TnI concentrations well below the upper reference limit provide further prognostic value for all patients with COPD when added to established risk assessments.

Correspondence between Capnovolumetric and Conventional Lung Function Parameters in the Diagnosis of Obstructive Airway Diseases.

BACKGROUND: Capnovolumetry is of interest as a method for the diagnosis of obstructive airway diseases, requiring little cooperation from the patient. OBJECTIVE: To help in the interpretation of capnovolumetric parameters, we aimed to identify their correspondence to conventional lung function indices. METHODS: We studied 978 patients from a diagnostic study with complete functional data and the clinical diagnosis of asthma, chronic obstructive pulmonary disease (COPD), or no respiratory disease. Using path analysis, four capnovolumetric parameters (slope of expiratory phase 3, ratio of slopes of phases 3 and 2, volume of phase 2, and the ratio area/volume of phase 3) previously identified as predictors of airway obstruction in terms of spirometry and body ple-thysmography, were analyzed regarding their relationship to each other and the diagnostic categories of asthma or COPD versus control, or obstruction versus no obstruction. We then identified four lung function parameters showing relationships as much as possible isomorphic to those between capnovolumetric parameters. RESULTS: The four capnovolumetric parameters were related to COPD and obstruction via both direct and indirect influences, but only two of them to asthma. Regarding the correspondence to lung function parameters, the slope of expiratory phase 3 corresponded best to the ratio of residual volume to total lung capacity, the ratio of slopes of phases 3 and 2 to forced expiratory volume in 1 s, the volume of phase 2 to forced expired flow at 50% of vital capacity, and the ratio area/volume of phase 3 to forced vital capacity. CONCLUSIONS: Our results indicated an intricate relationship of capnovolumetric parameters to each other and to airway obstruction, asthma, or COPD. The correspondence to conventional lung function measures seemed to reflect the entities lung hyperinflation, overall ventilatory impairment, bronchoconstriction, and ventilated lung volume, in that order. These findings might be helpful for clinicians in the interpretation of capnovolumetry.

Health-related quality of life associates with change in FEV1 in COPD: results from the COSYCONET cohort.

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.