Publications by authors named "Bernd Lamprecht"

64 Publications

Serum Tumor Marker Dynamics as Predictive Biomarkers in NSCLC Chemo-Immunotherapy and Mono-Immunotherapy Maintenance: A Registry-Based Descriptive Study.

Lung Cancer (Auckl) 2020 18;11:113-121. Epub 2020 Dec 18.

Johannes Kepler University Hospital, Department of Pulmonology, Linz, Austria.

Objective: To evaluate serum tumor markers (STM) as predictive biomarkers in advanced non-small cell lung cancer (NSCLC) treated with chemo-immunotherapy.

Methods: Patients having received platinum-based chemo-(CHT) and PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) combination therapy were retrospectively followed. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis. The marker with the highest relative elevation was defined "leading STM", its change was assessed between CHT-ICI as well as mono-ICI maintenance initiation and the respective subsequent restaging. Corresponding computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST). For CHT-ICI combination and subsequent mono-ICI-maintenance therapy, leading STM and RECIST response were evaluated regarding progression-free (PFS) and overall survival (OS) in Kaplan-Meier analyses.

Results: Among 80 CHT-ICI patients (41% women, mean age 63 years), median PFS was 5 months (M;4,9), median OS was 15M (10,/). PFS was significantly (p=0.042) longer, when the leading STM had decreased at first restaging under CHT-ICI combination therapy (9M (5,12; n=41) vs 5M (3,6; n=16)). In the 54 (67.5%) patients who received subsequent mono-ICI maintenance therapy, STM decrease was similarly associated with significantly (p<0.001) longer PFS (16M (7,/; n=16) vs 3.5M (2,6; n=22)). Patients with radiologically stable or progressive disease and concomitant leading STM decrease had similar PFS in the CHT-ICI combination phase (4M (3,7; n=16) vs 4.5M (2,6; n=14)), but longer PFS in the mono-ICI maintenance setting (13M (7,16; n=10) vs 3M (2,4; n=17)). Median OS was not reached in most subgroups.

Conclusion: Leading STM dynamics provide predictive biomarker information additional to radiological response evaluation patients receiving CHT-ICI combination therapy, especially in the mono-ICI maintenance setting.
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http://dx.doi.org/10.2147/LCTT.S286228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755331PMC
December 2020

Myocardial injury in severe COVID-19 is similar to pneumonias of other origin: results from a multicentre study.

ESC Heart Fail 2021 02 17;8(1):37-46. Epub 2020 Dec 17.

Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.

Aims: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes.

Methods And Results: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher.

Conclusions: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.
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http://dx.doi.org/10.1002/ehf2.13136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835505PMC
February 2021

Acute Exposure to Environmental Tobacco Smoke: A Controlled Study in Adults with Asthma.

Respiration 2020 Dec 9:1-8. Epub 2020 Dec 9.

Institute of Ecomedicine, Paracelsus Medical University, Salzburg, Austria.

Background: Short-term, indoor exposure to environmental tobacco smoke (ETS) is still highly prevalent; however, little is known about the acute lung response in adult asthma.

Objectives: We investigated whether acute, experimental ETS exposure influences symptoms, lung function, and inflammatory parameters.

Methods: Human subjects with asthma (n = 23) were exposed for 180 min to either room air or ETS at 250, 450, or 850 µg/m3. Respiratory symptoms, lung function, and exhaled nitric oxide (FeNO) were measured. Additionally, blood samples were analyzed for pro- and anti-inflammatory cytokines.

Results: Humans with asthma demonstrate an increase in respiratory symptoms at all levels of ETS exposure, while the forced expiratory volume in 1 s (FEV1) and FeNO decrease with increasing ETS. The anti-inflammatory cytokine interleukin (IL)-10 increases at intermediate ETS concentrations, whereas tumor necrosis factor (TNF)-α and IL-8 increase only at the highest ETS concentration.

Conclusion: Following 180 min of acute, experimental ETS exposure, we observed a significant increase in respiratory symptoms, a decrease in lung function, and an increase in inflammatory cytokines, indicating an acute lung response in asthma.
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http://dx.doi.org/10.1159/000508397DOI Listing
December 2020

Computed tomography findings as determinants of pulmonary function tests in fibrotic interstitial lung diseases-Network-analyses and multivariate models.

Chron Respir Dis 2020 Jan-Dec;17:1479973120967025

Department of Pulmonology, Kepler University Hospital GmbH, Johannes Kepler University Linz, Linz, Austria.

The aim was to evaluate the impact of multiple high-resolution computed tomography (HRCT) features on pulmonary function test (PFT) biomarkers in fibrotic interstitial lung disease (FILD) patients. HRCT of subsequently ILD-board-discussed FILD patients were semi-quantitatively evaluated in a standardized approach: 18 distinct lung regions were scored for noduli, reticulation, honeycombing, consolidations, ground glass opacities (GGO), traction bronchiectasis (BRK) and emphysema. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, diffusion capacity for carbon monoxide (DLCO) and transfer coefficient (KCO) were assessed. Interactions between each PFT biomarker and all HRCT scores were visualized by network analyses, modeled according to the Schwarz Bayesian Information Criterion and incorporated in uni- and multivariate stepwise regression analyses. Among 108 FILD patients (mean age 67 years, 77% male), BRK extent was a major significant uni- or multivariate determinant of all PFT analyzed. Besides that, diffusion-based variables DLCO and KCO showed a larger dependency on reticulation, emphysema and GGO, while forced expiratory volume-based measures FEV1, FVC and FEV1/FVC were more closely associated with consolidations. For TLC, the only significant multivariate determinant was reticulation. In conclusion, PFT biomarkers derived from spirometry, body plethysmography and diffusion capacity in FILD patients are differentially influenced by semi-quantified HRCT findings.
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http://dx.doi.org/10.1177/1479973120967025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720309PMC
December 2020

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data.

ERJ Open Res 2020 Oct 2;6(4). Epub 2020 Nov 2.

Pneumology Dept, Hospital Universitario de la Princesa, Instituto de Investigación Hospital Universitario de la Princesa (IISP), Universidad Autónoma de Madrid, Madrid, Spain.

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system.
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http://dx.doi.org/10.1183/23120541.00253-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682666PMC
October 2020

Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD: AIRFLOW-2.

Int J Chron Obstruct Pulmon Dis 2020 5;15:2807-2816. Epub 2020 Nov 5.

Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Purpose: COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization.

Patients And Methods: TLD was performed in COPD patients (FEV 30-60% predicted, CAT≥10 or mMRC≥2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed.

Results: Eighty-two subjects (FEV 41.6±7.4% predicted, 50.0% male, age 63.7±6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups.

Conclusion: In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD.

Clinical Trial Registration: NCT02058459.
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http://dx.doi.org/10.2147/COPD.S267409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652218PMC
November 2020

Impact of exercise training and supplemental oxygen on submaximal exercise performance in patients with COPD.

Scand J Med Sci Sports 2021 Mar 20;31(3):710-719. Epub 2020 Nov 20.

Institute of Sports Medicine, Prevention and Rehabilitation and Research Institute for Molecular Sports Medicine and Rehabilitation, Paracelsus Medical University Salzburg, Salzburg, Austria.

Functional impairment caused by chronic obstructive pulmonary disease (COPD) impacts on activities of daily living and quality of life. Indeed, patients' submaximal exercise capacity is of crucial importance. It was the aim of this study to investigate the effects of an exercise training intervention with and without supplemental oxygen on submaximal exercise performance. This is a secondary analysis of a randomized, controlled, double-blind, crossover trial. 29 COPD patients (63.5 ± 5.9 years; FEV 46.4 ± 8.6%) completed two consecutive 6-week periods of high-intensity interval cycling and strength training, which was performed three times/week with either supplemental oxygen or medical air (10 L/min). Submaximal exercise capacity as well as the cardiocirculatory, ventilatory, and metabolic response were evaluated at isotime (point of termination in the shortest cardiopulmonary exercise test), at physical work capacity at 110 bpm of heart rate (PWC 110), at the anaerobic threshold (AT), and at the lactate-2 mmol/L threshold. After 12 weeks of exercise training, patients improved in exercise tolerance, shown by decreased cardiocirculatory (heart rate, blood pressure) and metabolic (respiratory exchange ratio, lactate) effort at isotime; ventilatory response was not affected. Submaximal exercise capacity was improved at PWC 110, AT and the lactate-2 mmol/L threshold, respectively. Although supplemental oxygen seems to affect patients' work rate at AT and the lactate-2 mmol/L threshold, no other significant effects were found. The improved submaximal exercise capacity and tolerance might counteract patients' functional impairment. Although cardiovascular and metabolic training adaptations were shown, ventilatory efficiency remained essentially unchanged. The impact of supplemental oxygen seems less important on submaximal training effects.
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http://dx.doi.org/10.1111/sms.13870DOI Listing
March 2021

Impact of PET/CT for Assessing Response to Immunotherapy-A Clinical Perspective.

J Clin Med 2020 Oct 28;9(11). Epub 2020 Oct 28.

Institute of Nuclear Medicine and Endocrinology, Johannes Kepler University Hospital Linz, Kepler University Hospital GmbH, Altenberger Strasse 69, 4040 Linz and Krankenhausstrasse 9, 4020 Linz, Austria.

Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.
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http://dx.doi.org/10.3390/jcm9113483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694130PMC
October 2020

Nontuberculous Mycobacterial Pulmonary Disease from Mycobacterium hassiacum, Austria.

Emerg Infect Dis 2020 11;26(11):2776-2778

The clinical relevance of newly described nontuberculous mycobacteria is often unclear. We report a case of pulmonary infection caused by Mycobacterium hassiacum in an immunocompetent patient in Austria who had chronic obstructive pulmonary disease. Antimicrobial drug susceptibility testing showed low MICs for macrolides, aminoglycosides, fluoroquinolones, tetracyclines, imipenem, and linezolid.
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http://dx.doi.org/10.3201/eid2611.191718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588525PMC
November 2020

[Is there a post-COVID syndrome?]

Authors:
Bernd Lamprecht

Pneumologe (Berl) 2020 Oct 8:1-4. Epub 2020 Oct 8.

Klinik für Lungenheilkunde, Kepler Universitätsklinikum GmbH, Krankenhausstr. 9, 4020 Linz, Österreich.

For critically ill COVID-19 patients surviving the acute phase of the disease could possibly only mean having overcome the first stage of a long and challenging path. Physical, cognitive and psychological consequences seem to be realistic; however, do residual symptoms in patients who have returned to microbiological normalization constitute a post-COVID syndrome and which symptoms are principally possible in this context and are able to cause such a syndrome? It is no novelty that critically ill patients often still sustain functional limitations over a long period after discharge from hospital, in many cases even over many years. In most cases of COVID-19 it is too early for the diagnosis of a post-COVID syndrome. For this the symptoms would have to have lasted over a period of at least 6 months; therefore, only a post-infection fatigue can currently be spoken of. On top of this, even if patients recover physically they could be at particular risk of suffering from long-term mental health problems or perceive a reduced quality of life. Such findings exist not only after ARDS as many intensive care unit patients sustain long-term disorders, which is also known as post-intensive care syndrome (PICS). To sum up, there is sufficient evidence for the possible existence of a post-COVID syndrome or for the justification to correspondingly designate these possible sequelae with persisting symptoms in this way. In any case, all efforts that enable a complete functional recovery and a return to a life after corona are justified.
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http://dx.doi.org/10.1007/s10405-020-00347-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543035PMC
October 2020

Fatal case of COVID-19 in a 27-year-old woman with diabetes mellitus.

Wien Klin Wochenschr 2020 11 7;132(21-22):695-696. Epub 2020 Oct 7.

Department of Pulmonology, Kepler University Hospital and Johannes Kepler University, Linz, Austria.

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http://dx.doi.org/10.1007/s00508-020-01748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538535PMC
November 2020

[Masterplan 2025 of the Austrian Society of Pneumology (ASP)-the expected burden and management of respiratory diseases in Austria].

Wien Klin Wochenschr 2020 Sep;132(Suppl 3):89-113

Klinik für Lungenheilkunde, Kepler Universitätsklinikum, Linz, Österreich.

Scientific Members of the Austrian Society of Pneumology describe the expected development in respiratory health and provide guidance towards patient-oriented and cost-efficient respiratory care in Austria.Methods: In November 2017, respiratory care providers (physicians, nurses, physiotherapists) together with patient's advocacy groups and experts in health development, collaborated in workshops on: respiratory health and the environment, bronchial asthma and allergy, COPD, pediatric respiratory disease, respiratory infections, sleep disorders, interventional pneumology, thoracic oncology and orphan diseases.Results: Respiratory disease is extremely prevalent and driven by ill-health behavior, i.e. cigarette smoking, over-eating and physical inactivity. For the majority of respiratory diseases increased prevalence, but decreased hospitalizations are expected.The following measures should be implemented to deal with future challenges:1. Screening and case-finding should be implemented for lung cancer and COPD.2. E-health solutions (telemedicine, personal apps) should be used to facilitate patient management.3. Regional differences in respiratory care should be reduced through E‑health and harmonization of health insurance benefits across Austria.4. Patient education and awareness, to reduce respiratory health illiteracy should be increased, which is essential for sleep disorders but relevant also for other respiratory diseases.5. Respiratory care should be inter-professional, provided via disease-specific boards beyond lung cancer (for ILDs, sleep, allergy)6. Programs for outpatient's pulmonary rehabilitation can have a major impact on respiratory health.7. Increased understanding of molecular pathways will drive personalized medicine, targeted therapy (for asthma, lung cancer) and subsequently health care costs.
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http://dx.doi.org/10.1007/s00508-020-01722-wDOI Listing
September 2020

Results of the Austrian National Lung Cancer Audit.

Clin Med Insights Oncol 2020 10;14:1179554920950548. Epub 2020 Sep 10.

Second Department of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria.

Objectives: The Austrian Lung Cancer Audit (ALCA) is a pilot study to evaluate clinical and organizational factors related to lung cancer care across Austria.

Materials And Methods: The ALCA is a prospective, observational, noninterventional cohort study conducted in 17 departments in Austria between September 2013 and March 2015. Participating departments were selected based on an annual case load of >50 patients with lung cancer.

Results: The ALCA included 745 patients, representing 50.5% of all newly diagnosed cancer cases during that time period. In 75.8% of patients, diagnosis was based on histology, and in 24.2% on cytology; 83.1% had non-small-cell lung cancer, 16.9% small-cell lung cancer; and only 4.6% had to be classified as not otherwise specified cancers. The median time elapsed between first presentation at hospital and diagnosis was 8 days (interquartile range [IQR]: 4-15; range: 0-132); between diagnosis and start of treatment it was 15 days for chemotherapy (IQR: 9-27; range: 0-83), 21 days (IQR: 10-35; range: 0-69) for radiotherapy, and 24 days (IQR: 11-36; range: 0-138) for surgery, respectively. In 150 patients undergoing surgical treatment, only 3 (2.0%; n = 147, 3 missings) were seen with postoperative restaging indicating unjustified surgery. One-year follow-up data were available for 723 patients, indicating excellent 49.8% survival; however, a wide range of survival between departments (range: 37.8-66.7) was seen.

Conclusions: The ALCA conducted in high case load departments indicated management of lung cancer in accordance with international guidelines, and overall excellent 1-year survival.
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http://dx.doi.org/10.1177/1179554920950548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488615PMC
September 2020

Sex differences between women and men with COPD: A new analysis of the 3CIA study.

Respir Med 2020 09 13;171:106105. Epub 2020 Aug 13.

Hospital Universitario de la Princesa, Madrid, Spain. Electronic address:

Background: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females.

Methods: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis.

Results: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV%, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69-1.96) and 1.73 (1.50-2.00), respectively.

Conclusions: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients.
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http://dx.doi.org/10.1016/j.rmed.2020.106105DOI Listing
September 2020

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Stroke 2020 09 9;51(9):e254-e258. Epub 2020 Jul 9.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom (G.Y.H.L.).

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), =0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], <0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.
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http://dx.doi.org/10.1161/STROKEAHA.120.031208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359900PMC
September 2020

Systemic Inflammation, Vascular Function, and Endothelial Progenitor Cells after an Exercise Training Intervention in COPD.

Am J Med 2021 Mar 8;134(3):e171-e180. Epub 2020 Aug 8.

University Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus Medical University of Salzburg, Austria; Research Institute for Molecular Sports Medicine and Rehabilitation, Paracelsus Medical University of Salzburg, Austria. Electronic address:

Background: Exercise training is a cornerstone of the treatment of chronic obstructive pulmonary disease (COPD) in all disease stages. Data about the training effects with supplemental oxygen in nonhypoxemic patients remains inconclusive. In this study we set out to investigate the training and oxygen effects on inflammatory markers, vascular function, and endothelial progenitor cells in this population of increased cardiovascular risk.

Methods: In this prospective, randomized, double-blind, crossover study, 29 patients with nonhypoxemic COPD performed combined endurance and strength training 3 times a week while breathing medical air or supplemental oxygen for the first 6-week period, and were then reallocated to the opposite gas for the following 6 weeks. Exercise capacity, inflammatory biomarkers, endothelial function (peripheral arterial tone analysis), and endothelial progenitor cells were assessed. Data were also analyzed for a subgroup with endothelial dysfunction (reactive hyperemia index <1.67).

Results: Following 12 weeks of exercise training, patients demonstrated a significant improvement of peak work rate and an associated decrease of blood fibrinogen and leptin. Eosinophils were found significantly reduced after exercise training in patients with endothelial dysfunction. In this subgroup, peripheral arterial tone analysis revealed a significant improvement of reactive hyperemia index. Generally, late endothelial progenitor cells were found significantly reduced after the exercise training intervention. Supplemental oxygen during training positively influenced the effect on exercise capacity without impact on inflammation and endothelial function.

Conclusions: This is the first randomized controlled trial in patients with COPD to show beneficial effects of exercise training not only on exercise capacity, but also on systemic/eosinophilic inflammation and endothelial dysfunction.
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http://dx.doi.org/10.1016/j.amjmed.2020.07.004DOI Listing
March 2021

Quality of Life and Limitations in Daily Life of Stable COPD Outpatients in a Real-World Setting in Austria - Results from the CLARA Project.

Int J Chron Obstruct Pulmon Dis 2020 12;15:1655-1663. Epub 2020 Jul 12.

Department of Pulmonology, Kepler University Hospital, Linz, Austria.

Background: COPD patients suffer from respiratory symptoms and limitations in daily life. We aimed to characterize the impact of disease on overall health, daily life, and perceived well-being in COPD outpatients.

Methods: We conducted a national, cross-sectional study among pulmonologists and general practitioners (GPs). The St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) was used. Inclusion criteria were a physician's diagnosis of COPD and age ≥40 years. Subjects with a history of lung surgery, lung cancer or COPD exacerbation within the last four weeks were excluded.

Results: Sixty-seven pulmonologists and 6 GPs enrolled 1175 COPD patients. Two hundred forty-eight of those did not fulfill GOLD criteria for COPD (FEV/FVC <0.7) and 77 were excluded due to missing data. Finally, 850 patients (62.8% men; mean age 66.2 ± 0.3 (SE) years; mean FEV%pred. 51.5 ± 0.6 (SE)) were analyzed. Last year, 55.4% reported at least one exacerbation, and 12.7% were hospitalized for COPD exacerbation. Mean SGRQ-C total score was 43.1 ± 0.83 (SE) and mean component scores for symptoms, activity and impacts were 55.6, 55.4 and 30.5, respectively. Half of the patients (50.3%) reported not being able to do any sports and 78.7% stated that their respiratory symptoms did not allow them doing anything they would like to do. In patients with less severe COPD (FEVpred ≥50% and non-frequent exacerbations), global health status was overrated, ie, estimated as better by the physician than by the patient, while it was underrated in more severe COPD.

Conclusion: In Austria, the burden of disease in COPD outpatients tends to be underestimated in patients with milder airway obstruction and less exacerbations and overestimated in patients with more severe airway obstruction and frequent exacerbations. Our finding suggests that validated assessment of global health status might decrease these differences of perception.
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http://dx.doi.org/10.2147/COPD.S252033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367938PMC
July 2020

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020) : Statement of the Austrian Society of Pneumology (ASP).

Wien Klin Wochenschr 2020 Jul;132(13-14):365-386

Division of Paediatric Pulmonology and Allergology, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria.

The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV‑2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.
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http://dx.doi.org/10.1007/s00508-020-01691-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291190PMC
July 2020

COPD: Should Diagnosis Match Physiology?

Chest 2020 02;157(2):473-475

Department of Pulmonology, Kepler University Hospital, Linz, Austria; Faculty of Medicine, Johannes-Kepler-University, Salzburg, Austria.

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http://dx.doi.org/10.1016/j.chest.2019.09.039DOI Listing
February 2020

Therapy Line and Associated Predictors of Response to PD-1/PD-L1-Inhibitor Monotherapy in Advanced Non-small-Cell Lung Cancer: A Retrospective Bi-centric Cohort Study.

Target Oncol 2019 12;14(6):707-717

Department of Pulmonology, Kepler University Hospital Linz, Krankenhausstrasse 9, 4020, Linz, Austria.

Background: Evidence on PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy for advanced non-small-cell lung cancer (NSCLC) is mainly based on clinical trials in first- or second-line settings.

Objective: We aimed to investigate response and prognostic factors with special regard to third- or later-line therapy.

Patients And Methods: We retrospectively analyzed all patients who had received ICI monotherapy with nivolumab, pembrolizumab, or atezolizumab for advanced NSCLC. Computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST, version 1.1). Kaplan-Meier analyses were conducted to calculate progression-free (PFS) and overall (OS) survival; the impact of influencing variables was evaluated using uni- and multivariate Cox-regression analyses.

Results: Among 153 patients (59% men, mean age 66 years), median PFS was 4 months [mo; 95% confidence interval (95% CI) 3-5], OS was 13 mo (10-17), and objective response rate (ORR) was 22%. Therapy line ≥ 3 was associated with significantly inferior PFS (p = 0.003) and OS (p = 0.001). In first-line therapy PFS, OS, and ORR were 7 mo (3-11), 17 mo [9-not evaluable (n.e.)], and 36%; in second-line 4 mo (3-7), 18 mo (13-n.e.) and 19%, and in ≥ third-line 2 mo (1-3), 9 mo (4-12), and 13%. PFS was significantly influenced by PD-L1 expression in first-line therapy (p = 0.006). In ≥ third-line patients, Eastern Cooperative Oncology Group (ECOG) performance status significantly affected PFS and OS (both p < 0.001).

Conclusions: Third- or later-line single-agent anti-PD-1/PD-L1 therapy is less efficacious as compared to first- and second-line treatment. In that setting, ECOG performance status predominates known predictors like PD-L1 expression or presence of an alteration in EGFR or ALK.
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http://dx.doi.org/10.1007/s11523-019-00679-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875512PMC
December 2019

Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial.

Am J Respir Crit Care Med 2019 12;200(12):1477-1486

Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik Floridsdorf, Vienna, Austria.

Targeted lung denervation (TLD) is a bronchoscopic radiofrequency ablation therapy for chronic obstructive pulmonary disease (COPD), which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion. To determine the safety and impact of TLD on respiratory adverse events. We conducted a multicenter, randomized, sham bronchoscopy-controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, ≥2; or COPD Assessment Test score, ≥10) COPD (FEV, 30-60% predicted). The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization (defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention). Blinding was maintained through 12.5 months. Eighty-two patients (50% female; mean ± SD: age, 63.7 ± 6.8 yr; FEV, 41.6 ± 7.3% predicted; modified Medical Research Council dyspnea scale score, 2.2 ± 0.7; COPD Assessment Test score, 18.4 ± 6.1) were randomized 1:1. During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%,  = 0.008; odds ratio, 0.19; 95% confidence interval, 0.0750-0.4923,  = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%;  = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (hazard ratio, 0.35; 95% confidence interval, 0.13-0.99;  = 0.039). There was no statistical difference in the time to first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up. Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.Clinical trial registered with www.clinicaltrials.gov (NCT02058459).
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http://dx.doi.org/10.1164/rccm.201903-0624OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909835PMC
December 2019

Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC-A retrospective cohort study.

Lung Cancer 2019 08 31;134:59-65. Epub 2019 May 31.

Department of Pulmonology, Kepler University Hospital Krankenhausstrasse 9, 4020 Linz, Austria(1).

Objectives: To evaluate serum tumor markers (STM) as biomarkers for treatment monitoring and prognosis in advanced non-small cell lung cancer (NSCLC) treated with single-agent PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy.

Materials And Methods: Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis, initially elevated markers were used for follow-up. Leading STM change between ICI initiation and first subsequent restaging as well as corresponding computed tomography evaluations according to response evaluation criteria in solid tumors (RECIST) were retrospectively analyzed regarding progression-free (PFS) and overall survival (OS). In uni- and multivariate stepwise Cox-regression analyses, STM and RECIST response were analyzed for their impact on PFS and OS together with other known prognostic patient and tumor characteristics.

Results: Among 84 patients (61% men, mean age 68 years), median PFS was significantly (p < 0.001) longer, when STM decreased (11 M (7,19) N = 37) than in case of increases (<2-fold: 6 M (3,8) N = 31; ≥2-fold: 2 M (1,2) N = 16). Patients with initial STM decrease had longer (p < 0.001) median OS (not reached) than with STM increase (<2-fold: 14 M (12,26); ≥2-fold: 4 M (3,7)). Patients with stable or progressive disease by RECIST and concomitant STM decrease had longer (p < 0.001) PFS and OS (8 M (4,14) and 18 M (10,n.e.) N = 24) than upon STM increase (PFS: 2 M (2,4); OS: 10 M (6,13) N = 42). Significant impact on PFS was shown for STM response (p < 0.001), RECIST response (p = 0.003) and PD-L1 status (p = 0.003). For OS, STM response (p < 0.001), presence of cerebral metastases (p = 0.036) and therapy line ≥3 (p = 0.001) were identified.

Conclusion: Decreasing leading STM at first restaging predict longer PFS and OS and identify patients with favorable outcomes among initial radiological non-responders in ICI treated NSCLC patients.
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http://dx.doi.org/10.1016/j.lungcan.2019.05.033DOI Listing
August 2019

Baseline Absolute Lymphocyte Count and ECOG Performance Score Are Associated with Survival in Advanced Non-Small Cell Lung Cancer Undergoing PD-1/PD-L1 Blockade.

J Clin Med 2019 Jul 10;8(7). Epub 2019 Jul 10.

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Paracelsus Medical University, 5020 Salzburg, Austria.

Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 1 versus ECOG ≤ 1, HR: 3.23, 95%CI: 1.58-6.60, = 0.001), baseline absolute lymphocyte count (ALC; high: >0.93 × 10/L versus low: ≤ 0.93 × 10/L, HR: 0.38, 95%CI: 0.23-0.62, < 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15-4.14, = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01-17.36, = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56-1.45, = 0.675), nor PD-L1 expression on tumor cells (≥1% versus <1%, HR: 0.68, 95%CI: 0.41-1.13, = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.
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http://dx.doi.org/10.3390/jcm8071014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678702PMC
July 2019

Airflow Obstruction and Cardio-metabolic Comorbidities.

COPD 2019 04 27;16(2):109-117. Epub 2019 May 27.

a CIRO+, Centre of expertise for chronic organ failure , Horn , the Netherlands.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and often co-exists with cardiovascular disease (CVD), hypertension and diabetes. This international study assessed the association between airflow obstruction and these comorbidities. 23,623 participants (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) in 33 centers in the Burden of Obstructive Lung Disease (BOLD) initiative were included. 10.4% of subjects had airflow obstruction. Self-reports of physician-diagnosed CVD (heart disease or stroke), hypertension and diabetes were regressed against airflow obstruction (post-bronchodilator FEV/FVC < 5th percentile of reference values), adjusting for age, sex, smoking (including pack-years), body mass index and education. Analyses were undertaken within center and meta-analyzed across centers checking heterogeneity using the I-statistic. Crude odds ratios for the association with airflow obstruction were 1.42 (95% CI: 1.20-1.69) for CVD, 1.24 (1.02-1.51) for hypertension, and 0.93 (0.76-1.15) for diabetes. After adjustment these were 1.00 (0.86-1.16) (I:6%) for CVD, 1.14 (0.99-1.31) (I:53%) for hypertension, and 0.76 (0.64-0.89) (I:1%) for diabetes with similar results for men and women, smokers and nonsmokers, in richer and poorer centers. Alternatively defining airflow obstruction by FEV/FVC < 2.5th percentile or 0.70, did not yield significant other results. In conclusion, the associations of CVD and hypertension with airflow obstruction in the general population are largely explained by age and smoking habits. The adjusted risk for diabetes is lower in subjects with airflow obstruction. These findings emphasize the role of common risk factors in explaining the coexistence of cardio-metabolic comorbidities and COPD.
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http://dx.doi.org/10.1080/15412555.2019.1614550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816478PMC
April 2019

External Validation and Recalculation of the CODEX Index in COPD Patients. A 3CIAplus Cohort Study.

COPD 2019 02 14;16(1):8-17. Epub 2019 Mar 14.

ak Instituto de Investigación Hospital Universitario de la Princesa (IISP), Universidad Autónoma de Madrid, Cátedra UAM-Linde , Madrid , Spain.

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25-75% 426-1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up.
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http://dx.doi.org/10.1080/15412555.2018.1484440DOI Listing
February 2019

Overdiagnosis of COPD in Subjects With Unobstructed Spirometry: A BOLD Analysis.

Chest 2019 08 31;156(2):277-288. Epub 2019 Jan 31.

Respiratory Epidemiology and Public Health Group, Imperial College, London, London, United Kingdom.

Background: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.

Methods: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV/FVC < 0.7).

Results: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.

Conclusions: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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http://dx.doi.org/10.1016/j.chest.2019.01.015DOI Listing
August 2019

Adherence to inhaled therapy and its impact on chronic obstructive pulmonary disease (COPD).

BMC Pulm Med 2018 Oct 19;18(1):163. Epub 2018 Oct 19.

Department of Pulmonology, Kepler University Hospital, Krankenhausstrasse 9, A4021, Linz, Austria.

Background: COPD is a treatable disease with increasing prevalence worldwide. Treatment aims to stop disease progression, to improve quality of life, and to reduce exacerbations. We aimed to evaluate the association of the stage of COPD on adherence to inhaled therapy and the relationship between adherence and COPD exacerbations.

Methods: A retrospective analysis of patients hospitalized for acute exacerbation of COPD in a tertiary care hospital in Upper Austria and discharged with a guideline conform inhaled therapy was performed. Follow-up data on medical utilization was recorded for the subsequent 24 months. Adherence to inhaled therapy was defined according to the percentage of prescribed inhalers dispensed to the patient and classified as complete (> 80%), partial (50-80%) or low (< 50%).

Results: Out of 357 patients, 65.8% were male with a mean age of 66.5 years and a mean FEV of 55.0%pred. Overall, 35.3% were current smokers, and only 3.9% were never-smokers. In 77.0% inhaled triple therapy (LAMA + LABA + ICS) was prescribed. 33.6% showed complete adherence to their therapy (33.2% in men, 34.4% in women), with a mean age of 67.0 years. Mean medication possession ratio by GOLD spirometry class I - IV were 0.486, 0.534, 0.609 and 0.755, respectively (p = 0.002). Hence, subjects with complete adherence to therapy had a significantly lower FEV compared to those with low adherence (49.2%pred. vs 59.2%pred., respectively; p <  0.001). The risk of exacerbations leading to hospitalization was 10-fold higher in GOLD spirometry class IV compared to GOLD spirometry class I, which was even more evident in multivariate analysis (OR 13.62).

Conclusion: Complete adherence to inhaled therapy was only seen in 33.6% and was higher among those with more severe COPD.

Trial Registration: Not applicable.
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http://dx.doi.org/10.1186/s12890-018-0724-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194635PMC
October 2018

Phenotypes of COPD in an Austrian population : National data from the POPE study.

Wien Klin Wochenschr 2018 Jun 24;130(11-12):382-389. Epub 2018 May 24.

Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Sanatoriumstraße 2, 1140, Vienna, Austria.

Background: Chronic obstructive pulmonary disease (COPD) represents a major global health problem; however, there are no data regarding clinical phenotypes of these patients in Austria.

Methods: This was an analysis from the Austrian cohort of the cross-sectional Phenotypes of COPD in Central and Eastern Europe (POPE) study, which was offered to patients with stable COPD in a real-life setting. Patients were recruited at 5 different outpatient facilities in 3 different provinces in Austria. All consecutive patients aged ≥40 years with a diagnosis of COPD confirmed by a post-bronchodilator forced expired volume in 1 s/forced vital capacity (FEV/FVC) ratio <0.7 during a stable state (≥4 weeks without exacerbation or worsening of any relevant comorbidities) were considered eligible. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analyses of differences in patient characteristics, symptom load, comorbidities, and pharmacological treatment.

Results: Among 283 patients fulfilling the inclusion criteria, 49.5% were considered non-exacerbators, 21.6% were classified as exacerbators with chronic bronchitis, 21.2% exacerbators without chronic bronchitis, and 7.8% were patients with an asthma-COPD overlap. Exacerbators had significantly higher prevalence of symptoms, lower lung function and exercise capacity, and a higher prevalence of comorbidities, such as heart failure and depression, compared with the other patient phenotypes. A large majority of patients with stable COPD in this cohort received inhaled triple therapy, irrespective of exacerbation history.

Conclusions: There were significant differences in COPD outcome measures between predefined phenotypes of COPD in this study. The majority of patients with stable COPD in this Austrian population were not treated according to current COPD guidelines. While non-exacerbators appear to have been overtreated, patients with an asthma-COPD overlap appear to have been undertreated.
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http://dx.doi.org/10.1007/s00508-018-1347-7DOI Listing
June 2018

Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease.

BMC Med 2018 03 2;16(1):33. Epub 2018 Mar 2.

Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, Room HRS G29, CH -8001, Zurich, Switzerland.

Background: External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD.

Methods: We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores.

Results: Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUC - AUC = 0.015 [95% confidence interval (CI) = -0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUC - AUC = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency.

Conclusions: Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research.
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http://dx.doi.org/10.1186/s12916-018-1013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833113PMC
March 2018