Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort.

BACKGROUND: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities. METHODS: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up. RESULTS: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year. CONCLUSION: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.

Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD-results from COSYCONET.

BACKGROUND: MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD. METHODS: The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable "recently diagnosed mild to moderate COPD" defined by GOLD grades 0-2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP. RESULTS: 655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0-4 (n = 1470 finally). CONCLUSION: In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD.

Characteristics and outcomes of patients hospitalized for infection with influenza, SARS-CoV-2 or respiratory syncytial virus in the season 2022/2023 in a large German primary care centre.

BACKGROUND: In 2022/2023, Influenza A and Respiratory Syncytial Virus (RSV) reappeared in hospitalized patients, which was in parallel to ongoing SARS-CoV-2 infections. The aim of our study was to compare the characteristics and outcomes of these infections during the same time. METHODS: We included patients of all ages with a positive polymerase chain reaction (PCR) test for Influenza A/B, RSV, or SARS-CoV-2 virus hospitalized in the neurological, internal or paediatric units of the RoMed Hospital Rosenheim, Germany, between October 1st 2022 and February 28th 2023. RESULTS: A total of 906 patients were included (45.6% female; median age 68.0 years; 21.9% Influenza A, 48.2% SARS-CoV-2, 28.3% RSV). Influenza B (0.2%) and co-infections (1.5%) played a minor role. In patients aged ≥ 18 years (n = 637, 71%), Influenza A, SARS-CoV-2 and RSV groups differed in age (median 72, 79, 76 years, respectively; p < 0.001). Comorbidities, particularly asthma and COPD, were most prevalent for RSV. 103 patients were admitted to the intensive care unit (ICU) (16.3% Influenza A, 15.3% SARS-CoV-2, 19.2% RSV; p = 0.649), 56 died (6.8% Influenza A, 9% SARS-CoV-2, 11.1% RSV; p = 0.496). RSV showed the highest frequencies of low-flow oxygen supplementation for admission and stay. Differences in the length of stay were minor (median 7 days). Conversely, in patients aged < 18 years (n = 261, 28,8%), 19.5%, 17.6% and 60.2% were in the Influenza A, SARS-CoV-2 and RSV groups, respectively; 0.4% showed Influenza B and 2.3% co-infections. 17 patients were admitted to ICU (3.9% Influenza A, 9.6% RSV, 0% SARS-CoV-2); none died. RSV showed the highest frequencies of high- and low-flow oxygen supplementation, SARS-CoV-2 the lowest. CONCLUSION: When comparing infections with Influenza, SARS-CoV-2 and RSV in the winter 2022/2023 in hospitalized adult patients, rates of ICU admission and mortality were similar. RSV showed the highest frequencies of obstructive airway diseases, and of oxygen supplementation. The latter was also true in children/adolescents, in whom RSV dominated. Thus, in the situation of declining importance of SARS-CoV-2, RSV showed a disease burden that was relatively higher than that from Influenza and SARS-CoV-2 across ages, and this might be relevant for the seasons coming.

Capnovolumetry in combination with clinical history for the diagnosis of asthma and COPD.

Capnovolumetry performed during resting ventilation is an easily applicable diagnostic tool sensitive to airway obstruction. In the present analysis, we investigated in which way capnovolumetric parameters can be combined with basic anamnestic information to support the diagnosis of asthma and COPD. Among 1400 patients of a previous diagnostic study, we selected 1057 patients with a diagnosis of asthma (n = 433), COPD (n = 260), or without respiratory disease (n = 364). Besides performing capnovolumetry, patients answered questions on symptoms and smoking status. Logistic regression analysis, single decision trees (CHAID), and ensembles of trees (random forest) were used to identify diagnostic patterns of asthma and COPD. In the random forest approach, area/volume of phase 3, dyspnea upon strong exertion, s3/s2, and current smoking were identified as relevant parameters for COPD vs control. For asthma vs control, they were wheezing, volume of phase 2, current smoking, and dyspnea at strong exertion. For COPD vs asthma, s3/s2 was the primary criterion, followed by current smoking and smoking history. These parameters were also identified as relevant in single decision trees. Regarding the diagnosis of asthma vs control, COPD vs control, and COPD vs asthma, the area under the curve was 0.623, 0.875, and 0.880, respectively, in the random forest approach. Our results indicate that for the diagnosis of asthma and COPD capnovolumetry can be combined with basic anamnestic information in a simple, intuitive, and efficient manner. As capnovolumetry requires less cooperation from the patient than spirometry, this approach might be helpful for clinical practice.

Associations of oxygenated hemoglobin with disease burden and prognosis in stable COPD: Results from COSYCONET.

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1-4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO2, PaO2, PaCO2, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO2, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85-4.15, p < 0.0001) for values <12.5 g/dL. For comparison, the hazard ratio for WBC > 8000/µL was 2.33 (95% CI: 1.60-3.39, p < 0.0001). In stable COPD, the concentration of oxygenated hemoglobin provided additional information on disease state, especially mortality risk. OxyHem can be calculated from hemoglobin concentration and oxygen saturation without the need for the measurement of PaO2. It thus appears well suited for clinical use with minimal equipment, especially for GPs.

The impact of COPD on polyneuropathy: results from the German COPD cohort COSYCONET.

BACKGROUND: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. METHODS: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. RESULTS: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. CONCLUSION: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

Combined effects of lung function, blood gases and kidney function on the exacerbation risk in stable COPD: Results from the COSYCONET cohort.

RATIONALE: Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. METHODS: We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. RESULTS: 1506 patients with stable COPD (GOLD grade 1-4; mean age 64.5 ±â€¯8.1 y; mean FEV1 54 ±â€¯18 %predicted, mean eGFR 82.3 ±â€¯16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. CONCLUSION: Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

Acute effects of hypertonic saline inhalation on nitric oxide pulmonary diffusing capacity in healthy adults.

We investigated acute effects of inhalation of hypertonic saline solution (HSS) and oxygen (O2, control exposure) on pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). In a randomized crossover study, 20 healthy, non-smoking subjects were allocated to short-term inhalation of HSS or O2. Spirometry [(forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] and combined single-breath DLNO-DLCO measurements were performed before and immediately after inhalation of either HSS or O2. Percent changes were presented as median values (interquartile range). After HSS inhalation, DLNO, FEV1 and FVC were decreased by -3.0% (-7.3, 0.5), -3.1% (-4.2, -1.6) and -1.2% (-3.3, 0.6), respectively (all P < 0.05), without significant effect on DLCO. No changes in spirometry and diffusing capacity were observed following O2 inhalation. Acute inhalation of HSS causes a slight decrease in membrane conductance, probably as a result of fluid imbalance at the alveolar surface and interstitial fluid accumulation, both of which could impair gas exchange.

Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: An experimental exposure study in human volunteers.

3D printers are increasingly run at home. Nanoparticle emissions from those printers have been reported, which raises the question whether adverse health effects from ultrafine particles (UFP) can be elicited by 3D printers. We exposed 26 healthy adults in a single-blinded, randomized, cross-over design to emissions of a desktop 3D printer using fused deposition modeling (FDM) for 1 hour (high UFP-emitting acrylonitrile butadiene styrene [ABS] vs low-emitting polylactic acid [PLA]). Before and after exposures, cytokines (IL-1ß, IL-6, TNF-α, INF-γ) and ECP in nasal secretions, exhaled nitric oxide (FeNO), urinary 8-isoprostaglandin F2α (8-iso PGF2α ), and self-reported symptoms were assessed. The exposures had no significant differential effect on 8-iso PGF2α and nasal biomarkers. However, there was a difference (P < .05) in the time course of FeNO, with higher levels after ABS exposure. Moreover, indisposition and odor nuisance were increased for ABS exposure. These data suggest that 1 hour of exposure to 3D printer emissions had no acute effect on inflammatory markers in nasal secretions and urine. The slight relative increase in FeNO after ABS printing compared to PLA might be due to eosinophilic inflammation from inhaled UFP particles. This possibility should be investigated in further studies using additional biomarkers and longer observation periods.

Psychological and cognitive effects of laser printer emissions: A controlled exposure study.

The possible impact of ultrafine particles from laser printers on human health is controversially discussed although there are persons reporting substantial symptoms in relation to these emissions. A randomized, single-blinded, cross-over experimental design with two exposure conditions (high-level and low-level exposure) was conducted with 23 healthy subjects, 14 subjects with mild asthma, and 15 persons reporting symptoms associated with laser printer emissions. To separate physiological and psychological effects, a secondary physiologically based categorization of susceptibility to particle effects was used. In line with results from physiological and biochemical assessments, we found no coherent, differential, or clinically relevant effects of different exposure conditions on subjective complaints and cognitive performance in terms of attention, short-term memory, and psychomotor performance. However, results regarding the psychological characteristics of participants and their situational perception confirm differences between the participants groups: Subjects reporting symptoms associated with laser printer emissions showed a higher psychological susceptibility for adverse reactions in line with previous results on persons with multiple chemical sensitivity or idiopathic environmental intolerance. In conclusion, acute psychological and cognitive effects of laser printer emissions were small and could be attributed only to different participant groups but not to differences in exposure conditions in terms of particle number concentrations.