GOLD-grade specific disease characterization and phenotyping of COPD using quantitative computed tomography in the nationwide COSYCONET multicenter trial in Germany.

INTRODUCTION: To apply quantitative computed tomography (QCT) for GOLD-grade specific disease characterization and phenotyping of air-trapping, emphysema, and airway abnormalities in patients with chronic obstructive pulmonary disease (COPD) from a nationwide cohort study. METHODS: As part of the COSYCONET multicenter study, standardized CT in ex- and inspiration, lung function assessment (FEV1/FVC) and clinical scores (BODE index) were prospectively acquired in 525 patients (192women, 327men, aged 65.7±8.5y) at risk for COPD and at GOLD1-4. QCT parameters total lung volume (TLV), emphysema index (EI), parametric response mapping (PRM) for emphysema (PRMEmph) and functional small airway disease (PRMfSAD), total airway volume (TAV), wall percentage (WP) and total diameter (TD) were computed using automated software. RESULTS: TLV, EI, PRMfSAD and PRMEmph increased incrementally with each GOLD grade (p<0.001). Aggregated WP5-10 of subsegmental airways was higher from GOLD1 to GOLD3 and lower again at GOLD4 (p<0.001), whereas TD5-10 was significantly dilated only in GOLD4 (p<0.001). 58 patients were phenotyped as 'non-airway non-emphysema type', 202 as 'airway type', 96 as 'emphysema type' and 169 as 'mixed type'. FEV1/FVC was best in 'non-airway non-emphysema type' compared to other phenotypes, while 'mixed type' had worst FEV1/FVC (p<0.001). BODE index was 0.56±0.72 in the 'non-airway non-emphysema type' and highest with 2.55±1.77 in 'mixed type' (p<0.001). CONCLUSION: QCT demonstrates increasing hyperinflation and emphysema dependent on GOLD grade, while airway wall thickening increases until GOLD 3 and airway dilatation occurs in GOLD4. QCT identifies four disease phenotypes with implications for lung function and prognosis.

Characterization and Mortality Risk of Impaired Left Ventricular Filling in COPD.

BACKGROUND: In COPD, impaired left ventricular (LV) filling might be associated with coexisting HFpEF or due to reduced pulmonary venous return indicated by small LV size. We investigate the all-cause mortality associated with small LV or HFpEF and clinical features discriminating between both patterns of impaired LV filling. METHODS: We performed transthoracic echocardiography (TTE) in patients with stable COPD from the COSYCONET cohort to define small LV as LVEDD below the normal range and HFpEF features according to recommendations of the European Society of Cardiology. We assessed the E/A and E/e' ratios, NT-pro-BNP, hs-Troponin I, FEV1, RV, DLCo, and discriminated patients with small LV from those with HFpEF features or no relevant cardiac dysfunction as per TTE (normalTTE). The primary outcome was all-cause mortality after four and a half year. RESULTS: In 1752 patients with COPD, the frequency of small LV, HFpEF-features, and normalTTE was 8%, 16%, and 45%, respectively. Patients with small LV or HFpEF features had higher all-cause mortality rates than patients with normalTTE, HR: 2.75 (95% CI: [1.54 - 4.89]) and 2.16 (95% CI: [1.30 - 3.61]), respectively. Small LV remained an independent predictor of all-cause mortality after adjusting for confounders including exacerbation frequency and measures of RV, DLCo, or FEV1. Compared to normalTTE, patients with small LV had reduced LV filling, as indicated by lowered E/A. Yet in contrast to patients with HFpEF-features, patients with small LV had normal LV filling pressure (E/e') and lower levels of NT-pro-BNP and hs-Troponin I. CONCLUSION: In COPD, both small LV and HFpEF-features are associated with increased all-cause mortality and represent two distinct patterns of impaired LV filling This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD. RESEARCH QUESTION: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD. METHODS: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses. RESULTS: Among 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density. INTERPRETATION: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

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.

Period of hospitalization and mortality in transferred versus non-transferred COVID-19 patients: results from Germany.

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.

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.

Effects of training flights of combat jet pilots on parameters of airway function, diffusing capacity and systemic oxidative stress, and their association with flight parameters.

BACKGROUND: Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (Gz) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations. METHODS: Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (VA), and diffusing capacities per volume (KCO, KNO) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2'-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used. RESULTS: DLNO, DLCO, KNO, KCO and VA were reduced (p < 0.001) after flights, mean ± SD changes being 2.9 ± 5.0, 3.2 ± 5.2, 1.5 ± 3.7, 1.9 ± 3.7 and 1.4 ± 3.1%, respectively, while FeNO decreased by 11.1% and the ratio of 8-OHdG to creatinine increased by 15.7 ± 37.8%. The reductions of DLNO (DLCO) were smaller (p < 0.001) than those of KNO (KCO). In repeated flights on different days, baseline values were restored. Amongst various flight parameters comprising Gz-forces and/or being indicative of positive pressure breathing and oxygenation support, the combination of long flight duration and high altitude appeared to be linked to greater changes in DLNO and DLCO. CONCLUSIONS: The pattern of reductions in diffusing capacities suggests effects arising from atelectasis and increased diffusion barrier, without changes in capillary blood volume. The decrease in exhaled endogenous NO suggests bronchial mucosal irritation and/or local oxidative stress, and the increase in urinary oxidized guanosine species suggests systemic oxidative stress. Although changes were small and not clinically relevant, their presence demonstrated physiological effects of real training flights in a modern 4th generation fighter jet.

Effect of Buteyko breathing technique on clinical and functional parameters in adult patients with asthma: a randomized, controlled study.

BACKGROUND: The established therapy of asthma might be supported by additional non-pharmaceutical measures, such as the Buteyko breathing technique (BBT); however, the available data are mixed. To clarify the effects of BBT in patients with asthma, we investigated whether it led to clinical improvements with correlation to functional parameters. METHODS: Using a randomized, controlled design, we studied two groups (n = 30 each) of patients with asthma under either BBT or usual therapy (UT) w/o BBT over a period of 3 months. The primary outcome comprised the voluntary control pause (CP) after 3 months, secondary outcomes an additional breathhold parameter, forced expiratory volume in 1 s (FEV1), capnovolumetry, exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ) and Nijmegen Questionnaire (NQ), and the use of medication (ß2-agonists; inhaled corticosteroids, ICS). RESULTS: CP showed significant time-by-group interaction [F(1,58.09) = 28.70, p < 0.001] as well as main effects for study group [F(1,58.27) = 5.91, p = 0.018] and time [F(1,58.36) = 17.67, p < 0.001]. ACQ and NQ scores were significantly (p < 0.05 each) improved with BBT. This was associated with reductions in the use of ß2-agonists and ICS (p < 0.05 each) by about 20% each. None of these effects occurred in the UT group. While FEV1 and the slopes of the capnovolumetric expiratory phases 2 and 3 did not significantly change, the capnovolumetric threshold volume at tidal breathing increased (p < 0.05) with BBT by about 10 mL or 10%, compared to baseline, suggesting a larger volume of the central airways. No significant changes were seen for FeNO. CONCLUSIONS: BBT was clinically effective, as indicated by the fact that the improvement in symptom scores and the small increase in bronchial volume occurred despite the significant reduction of respiratory pharmacotherapy. As the self-controlled Buteyko breathing therapy was well-accepted by the participants, it could be considered as supporting tool in asthma therapy being worth of wider attention in clinical practice. Trial registration Retrospectively registered on 10 March 2017 at ClinicalTrials.gov (NCT03098849).

Characteristics of Current Smokers versus Former Smokers with COPD and Their Associations with Smoking Cessation Within 4.5 Years: Results from COSYCONET.

Background: Many patients with chronic obstructive pulmonary disease (COPD) continue smoking. We used data from the "real-life" COSYCONET COPD cohort to evaluate whether these patients differed from patients with COPD who either had ceased smoking prior to inclusion or ceased during the follow-up time of the study. Methods: The analysis was based on data from visits 1-5 (covering 4.5 years), including all patients with the diagnosis of COPD who were either ex-smokers or smokers and categorized as GOLD 1-4 or the former GOLD 0 category. We compared the characteristics of smokers and ex-smokers at baseline (visit 1), as well as the course of lung function in the follow-up of permanent ex-smokers, permanent smokers and incident ex-smokers (smokers at visit 1 who ceased smoking before visit 5). We also identified baseline factors associated with subsequent smoking cessation. Results: Among 2500 patients who were ever-smokers, 660 were current smokers and 1840 ex-smokers at baseline. Smokers were younger than ex-smokers (mean 61.5 vs 66.0 y), had a longer duration of smoking but fewer pack-years, a lower frequency of asthma, higher forced expiratory volume in 1 sec (FEV1, 59.4 vs 55.2% predicted) and higher functional residual capacity (FRC, 147.7 vs 144.3% predicted). Similar results were obtained for the longitudinal subpopulation, comprising 713 permanent ex-smokers, 175 permanent smokers, and 55 incident ex-smokers. When analyzing the time course of lung function, higher FRC, lower FEV1 and the presence of asthma (p < 0.05 each) were associated with incident cessation prior to visit 5, while less airway obstruction was associated with smoking continuation. Conclusion: These findings, which were consistent in the cross-sectional and longitudinal analyses, suggest that lung hyperinflation was associated with being or becoming ex-smoker. Possibly, it is perceived by patients as one of the factors motivating their attempts to quit smoking, independent from airway obstruction.

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.

Clinical factors linked to the type of respiratory medication in COPD: results from the COSYCONET cohort.

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

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.

Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adults.

Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 µg/m³. A one interquartile range increase of 7 µg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

MRI Compared with Low-Dose CT for Incidental Lung Nodule Detection in COPD: A Multicenter Trial.

Purpose: To investigate morphofunctional chest MRI for the detection and management of incidental pulmonary nodules in participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: In this prospective study, 567 participants (mean age, 66 years ± 9 [SD]; 340 men) underwent same-day contrast-enhanced MRI and nonenhanced low-dose CT (LDCT) in a nationwide multicenter trial (clinicaltrials.gov: NCT01245933). Nodule dimensions, morphologic features, and Lung Imaging Reporting and Data System (Lung-RADS) category were assessed at MRI by two blinded radiologists, and consensual LDCT results served as the reference standard. Comparisons were performed using the Student t test, and agreements were assessed using the Cohen weighted κ. Results: A total of 525 nodules larger than 3 mm in diameter were detected at LDCT in 178 participants, with a mean diameter of 7.2 mm ± 6.1 (range, 3.1-63.1 mm). Nodules were not detected in the remaining 389 participants. Sensitivity and positive predictive values with MRI for readers 1 and 2, respectively, were 63.0% and 84.8% and 60.2% and 83.9% for solid nodules (n = 495), 17.6% and 75.0% and 17.6% and 60.0% for part-solid nodules (n = 17), and 7.7% and 100% and 7.7% and 50.0% for ground-glass nodules (n = 13). For nodules 6 mm or greater in diameter, sensitivity and positive predictive values were 73.3% and 92.2% for reader 1 and 71.4% and 93.2% for reader 2, respectively. Readers underestimated the long-axis diameter at MRI by 0.5 mm ± 1.7 (reader 1) and 0.5 mm ± 1.5 (reader 2) compared with LDCT (P < .001). For Lung-RADS categorization per nodule using MRI, there was substantial to perfect interreader agreement (κ = 0.75-1.00) and intermethod agreement compared with LDCT (κ = 0.70-1.00 and 0.69-1.00). Conclusion: In a multicenter setting, morphofunctional MRI showed moderate sensitivity for detection of incidental pulmonary nodules in participants with COPD but high agreement with LDCT for Lung-RADS classification of nodules.Clinical trial registration no. NCT01245933 and NCT02629432Keywords: MRI, CT, Thorax, Lung, Chronic Obstructive Pulmonary Disease, Screening© RSNA, 2023 Supplemental material is available for this article.

Development of a diagnostic score using FeNO and symptoms to predict asthma.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is known as effective for ruling-in asthma. The diagnostic value might be increased in combination with clinical signs and symptoms (CSS). The aim was to develop a new model for ruling-in and ruling-out asthma. METHODS: Diagnostic multi-centre study in three practices of pneumologists in Germany. Whole-body plethysmography was combined with bronchodilation tests or bronchial provocation as diagnostic reference standard. Follow-up was performed after 3 months. An expert committee evaluated test results, symptoms, and course of disease for the final diagnosis. Relevant CSS known from guidelines were used to enable combinatorial development of decision rules. Outcomes of multiple logistic regression modeling were translated into a diagnostic score and internally validated by ten-fold cross validation. RESULTS: 308 patients with complete follow-up were included. 186 (60.4%) were female, average age was 44.7 years and 161 (52.5%) had asthma. The average area under the receiver operating curve (AUC) of the diagnostic score was 0.755 (interquartile range 0.721-0.814). Allergic rhinitis, wheezing, dyspnea on exertion, coughing attacks at night, and awakening by shortness of breath were leading symptoms for ruling-in asthma. Frequent coughing and frequent respiratory infections were leading symptoms for ruling-out. The combination of FeNO and CSS allowed ruling-in asthma with a probability of up to 99%, and ruling-out with a post-test probability down to 9%. CONCLUSION: The diagnostic scoring model increased the diagnostic value of FeNO in combination with CSS. The new decision rule allowed to rule-in asthma with high certainty, and also to rule-out with acceptable certainty.

Oral inflammation and exhaled nitric oxide fraction: a cross-sectional study.

Oral inflammation is not associated with increased F ENO in nonasthmatic children and adolescents. The observed inverse association implies that gingival bleeding might decrease F ENO but this needs more study to be confirmed. https://bit.ly/3BhMP6f.

The impact of gingivitis reduction on lung function: a randomized trial under intensified oral hygiene.

BACKGROUND: Periodontal disease and lung function impairment were found to be associated with low-grade systemic or local inflammation, and it might be that gingival/periodontal inflammation triggers lung function due to systemic inflammation or the transfer of oral bacteria or its components to the lung. A recent observational study in non-smoking subjects showed that lung volumes and flow rates were significantly reduced by 71-185 ml for severe gingivitis regardless of the adjustment for potential confounders. The result did not show any confounding by smoking, and the association between gingivitis and lower lung function was not modified by systemic inflammation. The designed interventional trial primarily aims to test the hypothesis that gingivitis reduction by optimized daily oral hygiene, professional tooth cleaning and antibacterial chlorhexidine (CHX)-containing mouth rinse improves lung function in terms of forced vital capacity (FVC) by at least 2%. The secondary objective will test the hypothesis that gingivitis reduction improves forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75) by at least 2%. Furthermore, the influence of the oral microbiome will be taken into account. METHODS: The study has to include 120 non-smoking subjects aged between 18 and 30 years with biofilm-induced gingivitis. The chosen "waiting control group design" will compare the immediate intervention group with the delayed intervention group, which serves as a control group. Dental and gingival status, lung function and oral microbiome will be recorded. The intensified preventive intervention-professional tooth cleaning, one-stage full-mouth disinfection with CHX and safeguarding an optimal daily oral hygiene by each subject-cannot be blinded, but the outcome measurement in terms of lung function tests is blind. DISCUSSION: This proposed multidisciplinary study has several strengths. Only one previous intervention study with patients with severe periodontitis (mostly smokers) has been performed. It is novel to include non-smoking subjects with mild and potentially reversible oral inflammation. Furthermore, this research is innovative, because it includes evidence-based interventions for gingivitis reduction, standardized measures of the outcome on lung function and oral microbiome and combines expertise from dentistry, lung physiology, oral microbiology and epidemiology/statistical modelling. TRIAL REGISTRATION: German Clinical Trial Register DRKS00028176. Registered on February 2022.

The Diagnosis and Treatment of COPD and Its Comorbidities.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third most common cause of death around the world. The affected patients suffer not only from impaired lung function, but also from a wide variety of comorbidities. Their cardiac comorbidities, in particular, lead to increased mortality. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. RESULTS: The usual diagnostic criteria for COPD are a post-bronchodilator FEV1/FVC quotient below the fixed threshold of 0.7, or, preferably, below the lower limit of normal (LLN) according to the GLI reference values for the avoidance of over- and underdiagnosis. The overall prognosis is markedly affected by comorbidities of the lung itself and those that involve other organs; in particular, many persons with COPD die of heart disease. The potential presence of heart disease must be borne in mind in the evaluation of patients with COPD, as lung disease can impair the detection of heart disease. CONCLUSION: As patients with COPD are often multimorbid, the early diagnosis and adequate treatment not only of their lung disease, but also of their extrapulmonary comorbidities are very important. Well-established diagnostic instruments and well-tested treatments are available and are described in detail in the guidelines concerning the comorbidities. Preliminary observations suggest that more attention should be paid to the potential positive effects of treating comorbidities on the lung disease itself, and vice versa.

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.