Search

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20–94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6–7·0; p1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09–0·14; p

New findings What is the central question of this study? The study aimed to establish a novel model to study the chronic obstructive pulmonary disease (COPD)-related cardiopulmonary effects of dynamic hyperinflation in healthy subjects. What is the main finding and its importance? A model of expiratory resistance breathing (ERB) was established in which dynamic hyperinflation was induced in healthy subjects, expressed both by lung volumes and intrathoracic pressures. ERB outperformed existing methods and represents an efficacious model to study cardiopulmonary mechanics of dynamic hyperinflation without potentially confounding factors as present in COPD. Abstract Dynamic hyperinflation (DH) determines symptoms and prognosis of chronic obstructive pulmonary disease (COPD). The induction of DH is used to study cardiopulmonary mechanics in healthy subjects without COPD-related confounders like inflammation, hypoxic vasoconstriction and rarefication of pulmonary vasculature. Metronome-paced tachypnoea (MPT) has proven effective in inducing DH in healthy subjects, but does not account for airflow limitation. We aimed to establish a novel model incorporating airflow limitation by combining tachypnoea with an expiratory airway stenosis. We investigated this expiratory resistance breathing (ERB) model in 14 healthy subjects using different stenosis diameters to assess a dose-response relationship. Via cross-over design, we compared ERB to MPT in a random sequence. DH was quantified by inspiratory capacity (IC, litres) and intrinsic positive end-expiratory pressure (PEEPi, cmH2 O). ERB induced a stepwise decreasing IC (means (95% CI): tidal breathing: 3.66 (3.45-3.88), ERB 3 mm: 3.33 (1.75-4.91), 2 mm: 2.05 (0.76-3.34), 1.5 mm: 0.73 (0.12-1.58) litres) and increasing PEEPi (tidal breathing: 0.70 (0.50-0.80), ERB 3 mm: 11.1 (7.0-15.2), 2 mm: 22.3 (17.1-27.6), 1.5 mm: 33.4 (3.40-63) cmH2 O). All three MPT patterns increased PEEPi, but to a far lesser extent than ERB. No adverse events during ERB were noted. In conclusion, ERB was proven to be a safe and efficacious model for the induction of DH and might be used for the investigation of cardiopulmonary interaction in healthy subjects.

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 (FEV1/FVC

Background Increasing attention has been drawn on the assessment of body composition phenotypes, since the distribution of soft tissue influences cardio-metabolic risk. Dual-energy X-ray absorptiometry (DXA) is a validated technique to assess body composition. European reference values from population-based cohorts are rare. Aims To provide age- and sex-related reference values of body composition parameters and visceral adipose tissue (VAT) mass, and for lean mass index (LMI) with regard to fat mass index (FMI) quantities and BMI categories. Methods GE-Lunar Prodigy DXA scans of 10.894 participants, aged 18–81 years, recruited from 2011 to 2019 by the Austrian LEAD study, a population-based cohort study, have been used to construct reference curves using the LMS method. Parameters assessed are FMI, LMI, appendicular LMI, fat mass ratios android/gynoid and trunk/limbs, and VAT. Results All lean mass and fat mass parameters indicating central fat accumulation were higher in men, whereas other fat mass indices were higher in women. LMI differed between each FMI subgroup (low vs. normal, low vs. high, normal vs. high), and BMI category in all ages and LMI increased with FMI and BMI classes. VAT mass was higher in men compared with women and increased across all age groups within both sexes. Conclusion The present study provides age- and sex-related reference values for European adults aged 18–81 years for body composition parameters and VAT mass for Lunar Prodigy DXA. In addition, this study reports LMI reference values with regard to fat mass quantities, showing a positive association with increasing FMI percentiles and BMI categories., European Journal of Clinical Nutrition, 74 (8), ISSN:0954-3007, ISSN:1476-5640

The impact of body composition on the early origin of chronic diseases is an increasingly appreciated phenomenon. Little is known about the characteristics of children with varying body composition. The aim of this study was to investigate serum lipid profiles and other characteristics in relation to body composition. The data of 1394 participants (aged 6 to, Children, 8 (11), ISSN:2227-9067

Background: Sensitization to aero-allergens is a common condition worldwide and prevalence vary between countries tremendously (17%-69%). Sensitization is related to allergic disease conditions and conflicting data of associated factors exists. Therefore, we aimed to investigate 1.the prevalence of positive SPT including age and sex distribution and 2. associated factors with positive SPT in a broad-aged European general population Methods: 11.283 males and females aged from 6-82 yrs. from the Austrian LEAD general-population cohort have been included with aero-allergen SPT and assessments of socioeconomic status (SES), exposure to tobacco smoke, lifestyle habits, allergic and/or respiratory diseases, body composition, family medical history and pets in household. Results: Positive SPT was higher in males vs. females in both age groups (42.9% vs. 30.5% and 42.2% vs. 33.7%, p House dust mite and grasses mix were the most prevalent allergens in both age groups; however, associated factors with a positive SPT differed in the two age groups (Table1 and Table 2). Conclusion: We found that a positive SPT is a highly prevalent condition in the general population, more prevalent in males vs females, the main allergens are grasses mix and house dust mite, in both age groups. There is a difference in factors associated with SPT between childhood/adolescence and adulthood.

The second-generation ALK tyrosine kinase inhibitor brigatinib has recently been approved in the European Union for use after crizotinib treatment in patients with EML4-ALK-rearranged lung cancer. In the current study, brigatinib was investigated as second-line or later-line treatment in 35 patients who had developed resistance to crizotinib, ceritinib, or alectinib. Most patients (68.6%) received brigatinib as second or third line (range: second to 12th line). In the total cohort, complete and partial responses were obtained for 9.1 and 75.8%, respectively. Overall median progression-free survival was 9.9 months, whereas the largest treatment cohort (brigatinib after crizotinib failure) showed a median progression-free survival of 8.4 months. Fifty-four percent of patients with baseline brain metastases responded to brigatinib treatment. Brigatinib was highly effective after crizotinib and ceritinib failure. Six patients had received alectinib as monotherapy, second-line, or third line before brigatinib; of these, four experienced partial responses and two progressed responses. Brigatinib treatment was well tolerated.

Background Analysis of cell-free DNA from blood could provide an alternative method for identifying genomic changes in the tumors of patients with advanced lung adenocarcinoma. Objective We compared the performance of droplet digital PCR (ddPCR) and Cobas® EGFR Mutation Test v2 (Cobas) for detecting EGFR mutations in cell-free plasma DNA. Patients and Methods Plasma samples from patients with advanced EGFR-mutated lung adenocarcinoma were analyzed for EGFR T790M, exon 19 deletions, and L858R mutations by both ddPCR and Cobas. Results T790M testing was performed in 354 plasma samples collected from 129 patients. The concordance rate between ddPCR and Cobas for T790M, sensitivity, and specificity were 86, 100, and 85%, respectively. Exon 19 deletions were analyzed in 196 plasma samples obtained from 71 of the 129 patients using both platforms. The concordance rate between ddPCR and Cobas for exon 19 deletions, sensitivity, and specificity were 90, 92, and 89%, respectively. L858R mutations were studied in 124 plasma samples obtained from 44 of the 129 patients using both assays. The concordance rate between ddPCR and Cobas for L858R, sensitivity, and specificity were 90, 91, and 89%, respectively. In patients who progressed under treatment with an EGFR TKI (n = 50), the T790M positivity rate was 66% using ddPCR, but only 24% using Cobas. Conclusions We observed a high concordance between ddPCR and Cobas in detecting EGFR mutations in plasma samples of patients with advanced EGFR-mutated lung adenocarcinoma, but ddPCR was more sensitive than Cobas.

Background DXA is a widely used technique to assess body composition. Reference values based on a large general population cohort of European children and adolescents were missing. The aim of this study was to provide age‐ and sex‐specific reference percentiles of body composition parameters for European children and adolescents and to compare them to the American NHANES cohort. Additionally, exponents accounting best for height biases were analysed. Methods DXA scans of 1573 participants, aged 6 to 18 years, recruited from 2011 to 2019 by the Austrian LEAD study, a representative population‐based cohort, have been used to create reference charts using the LMS model. Results Reference charts displaying percentile curves and the corresponding reference values are provided. Fat mass parameters were higher in females, while lean mass parameters were higher in males. Compared to the NHANES cohort medians of FMI and LMI were always lower. For FMI , BMI , LMI and ALMI the best fitting exponent were 2.5, 3, 3 and 3.5 respectively Conclusions The present study provides reference charts for children and adolescents aged 6 to 18 years, for body composition parameters assessed by DXA. The charts enable comparison to a European general‐population cohort and indicate that reference populations should be chosen with caution., Pediatric Obesity, 16 (1)

Background Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems is often poor, leaving room for false positive and false negative results. However, conventional methods used to increase specificity decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the "Sensitivity Improved Two-Test" or "SIT2" algorithm. Methods SIT2 involves confirmatory re-testing of samples with results falling in a predefined retesting-zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT2 to single tests and orthogonal testing (OTA) in an Austrian cohort (1,117 negative, 64 post-COVID positive samples) and validated the algorithm in an independent British cohort (976 negatives, 536 positives). Results The specificity of SIT2 was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT2 when compared to single tests or OTA. SIT2 allowed correct identification of infected individuals even when a live virus neutralization assay could not detect antibodies. Compared to single testing or OTA, SIT2 significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. Conclusion For SARS-CoV-2 serology, SIT2 proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

Background: European population cohorts continue to expand our understanding of chronic airways disease and inter-study collaboration may help address the inevitable limitations of study size, duration, era and geography. Towards this aim, CADSET has collated data from ten major general population European cohorts: Asklepios; Copenhagen City Heart Study; Copenhagen General Population Study; ECRHS; HUNT; LEAD; Lifelines, OLIN, Rotterdam Study and WSAS. We included males and females aged 20 to 95 years with baseline demographic and spirometry data.Results: Data from 262,829 individuals (44% male) from multiple European countries provided good coverage across all adult ages (Fig.1A). Recruitment occurred in every year from 1976 through 2020. 23% were current-smokers and 42% were never-smokers, a pattern varying with advancing age (Fig.1B). The prevalence of airflow limitation varied according to whether lower limit of normal (LLN) or Interpretation: These results fit with previous reports, however the size, geographical reach and span of recruitment provided by this collaboration provides a unique opportunity to explore chronic airways disease development. Together, we are now pursuing research questions previously beyond the scope of individual cohort studies.

Rationale: Metabolic syndrome (MetS), in particular increased central obesity is associated with cardiovascular events but also lung function (LF) impairment. The aim was to investigate whether LF impairment is associated with increased levels of visceral adipose tissue (VAT). Methods: Data was obtained from the Austrian LEAD Study, an observational, population-based cohort study. Adults aged 25-82 years with valid LF and metabolic data, including waist circumference (WC) for central obesity, and DXA Scans for VAT (n=9.157) were included in this analysis. LF was assessed by spirometry pre- and post-bronchodilation (BD). Abnormal LF was defined as FEV1 pre BD Results: Table 1 shows odds ratios of MetS components and VAT associated with impaired LF pattern. Increased VAT was associated with both, obstructive (OR 1.5 [1.3-1.8]) and restrictive (OR 2.4 [1.8-3.0]) LF pattern, while increased WC was not. Conclusion: VAT showed a consistent association with LF impairment independent of the type of impairment, in contrast to the different components of the MetS.

Background: Perception of global health status may differ between COPD patients and their physicians. Methods: We conducted a national, cross-sectional study among pulmonologists and general practitioners in Austria. The St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C) was used. Furthermore, we asked, independent from each other, the patient as well as the treating physician to estimate the global health status of the patient (excellent, good, fair, poor, very poor). 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: Of 1,175 COPD patients, 248 did not fulfill the GOLD criteria for COPD (FEV1/FVC≥0.7) and 77 were excluded due to missing data. In 48.7% of study participants, patients and physicians disagreed on the global health status. In 29.7% it was estimated better by the physician than by the patient (overrated patients), and in 19.0% it was underrated. Multivariate regression analysis indicated that overrated patients had a statistically significant better lung function (FEV1), less exacerbations and a lower total SGRQ-C score compared to underrated patients. Conclusion: In stable COPD outpatients the global health status tends to be overestimated in patients with milder airway obstruction and less exacerbations and vice versa.

Background In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. Methods We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. Results All 3 assays presented with high specificities: 99.2% (98.6–99.7) for Abbott, 99.7% (99.2–100.0) for Roche, and 98.3% (97.3–98.9) for DiaSorin. In contrast to the manufacturers’ specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen’s Kappa 0.71–0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2–67.9), 77.6% (52.8–91.5), and 32.6% (23.6–43.1) for Abbott, Roche, and DiaSorin, respectively. Conclusion We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.

There is growing interest in blood eosinophil counts in the management of chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Despite this, typical blood eosinophil levels in the general population, and the impact of potential confounders on these levels have not been clearly defined.We measured blood eosinophil counts in a random sample of 11 042 subjects recruited from the general population in Austria. We then: 1) identified factors associated with high blood eosinophil counts (>75th percentile); and 2) excluded subjects with these factors to estimate median blood eosinophil counts in a “healthy” sub-population (n=3641).We found that: 1) in the entire cohort, age ≤18 years (OR 2.41), asthma (OR 2.05), current smoking (OR 1.72), positive skin prick test (OR 1.64), COPD (OR 1.56), metabolic syndrome (OR 1.41), male sex (OR 1.36) and obesity (OR 1.16) were significantly (pversus 100 (30–310) cells·µL−1, respectively) and did not change with age.Median blood eosinophil counts in adults are considerably lower than those currently regarded as normal, do not change with age beyond puberty, but are significantly influenced by a variety of factors which have an additive effect. These observations will contribute to the interpretation of blood eosinophil levels in clinical practice.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the major reason for COPD hospitalization and increased risk for readmissions. The organizational structure of Austrian hospitals provides the opportunity to investigate the impact of specialized respiratory care compared to general care on adherence to guidelines and readmission in AECOPD.The data from the European COPD audit, a prospective observational non-interventional cohort trial were analyzed. In total, 823 patients admitted due to AECOPD in 26 hospitals (specialized respiratory care vs. general care) within Austria were included. Patients characteristics and outcomes (length of stay, readmission rate, and mortality) were analyzed in relation to hospital resources (personnel and equipment) and adherence to international guidelines.Patients admitted to general care had more comorbidities (Charlson comorbidity index: 2.6 ± 1.7 vs. 2.0 ± 1.4; p 0.05) and a shorter length of stay (10.7 ± 7.8 days vs. 12.0 ± 10.2 days; p 0.05). Patients admitted to specialized respiratory care more often underwent blood gas analysis and non-invasive ventilation (98.4% vs. 81.5% and 68.6% vs. 26.7%, p 0.01; respectively). In multivariate analysis, the risk for AECOPD readmission was lower (odds ratio, OR 0.72 [0.51;0.91]; p 0.05) in patients admitted to specialized respiratory care.A greater adherence to COPD guidelines with respect to blood gas analysis and non-invasive ventilation and decreased AECOPD readmission risk was observed for patients admitted to specialized respiratory care. Adherence to guidelines may have the potential to decrease COPD readmission rates.

Background: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. Methods: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). Results: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. Conclusions: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.

Background Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1(c) levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes.Design This observational, population-based cohort study included 11.014 subjects aged 6-80 years. Examinations included blood samples, ankle-brachial index, ECG, dual-energy X-ray absorptiometry scan and an interviewer-administered questionnaire.Results Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6

Background and objective Cardiovascular risk is substantially increased in patients with COPD and can be quantified via arterial stiffness. The PDE-IV inhibitor roflumilast revealed a potential reduction of COPD-related cardiovascular risk. We aimed to investigate the effects of roflumilast on arterial stiffness by quantification of pulse wave velocity (PWV) in stable COPD. Methods In this randomized placebo-controlled trial, 80 COPD patients received roflumilast or placebo for 24 weeks. The primary outcome was the change in cf-PWV. Secondary outcomes comprised markers of vascular function (e.g. Aix and RHI), systemic inflammation (e.g. IL-6 and TNF-α) and clinical characteristics of COPD (e.g. CAT and 6MWT). Results A total of 33 and 34 patients completed the roflumilast and placebo arm, respectively (age, median (IQR): 64.5 (61-69.5) vs 64.5 (56-72) years; FEV1 , median (IQR): 34.5 (25.5-48.6) vs 35.3 (27-46.8) % predicted; 6MWT, median (IQR): 428 (340-558) vs 456 (364-570) m). Change from baseline PWV did not show a significant difference between roflumilast and placebo (+5.0 (95% CI: -2.0 to +13.0) vs 0.0 (95% CI: -7.0 to +7.0)%, P = 0.268). Roflumilast did not improve markers of vascular function or systemic inflammation. We observed a significant improvement in change from baseline 6MWT with roflumilast versus placebo (+53.0 (95% CI: +19.1 to +86.9) vs -0.92 (95% CI: -35.1 to +33.3) m, P = 0.026). Conclusion Our study revealed no beneficial effects of roflumilast on arterial stiffness. Further studies are needed to test a potential improvement of exercise capacity with roflumilast in COPD.

Background Acquired epidermal growth factor receptor (EGFR) T790M mutation is the primary resistance mechanism to first-generation EGFR tyrosine kinase inhibitors (TKIs) used in advanced, EGFR mutation-positive non-small-cell lung cancer (NSCLC). Available data, predominantly in Asian patients, suggest that this mutation is also the major cause of resistance to the irreversible ErbB family blocker, afatinib. For EGFR T790M-positive patients who progress on EGFR TKI therapy, osimertinib is an effective treatment option. However, data on osimertinib use after afatinib are, to date, scarce. Objective To identify the prevalence of EGFR T790M mutations in predominantly Caucasian patients with stage IV EGFR mutation-positive NSCLC who progressed on afatinib, and to investigate the subsequent response to osimertinib. Patients and Methods In this single-center, retrospective analysis, EGFR T790M mutation status after afatinib failure was assessed using liquid biopsy and tissue rebiopsy. EGFR T790M-positive patients subsequently received osimertinib. Results Sixty-seven patients received afatinib in the first-, second-, or third-line (80.6%, 14.9%, and 4.5%, respectively). After afatinib failure, the T790M mutation was identified in 49 patients (73.1%). Liquid biopsy and tissue rebiopsy were concordant in 79.4% of cases. All patients with T790M-positive tumors received osimertinib (73.5% after first-line afatinib); 37 (75.5%) of these had an objective response (complete response: 22.4%; partial response: 53.1%). Response rate was independent of T790M copy number. Conclusion EGFR T790M mutation is a major mechanism of acquired resistance to afatinib. Osimertinib confers high response rates after afatinib failure in EGFR T790M-positive patients and its use in sequence potentially allows extended chemotherapy-free treatment.

Introduction Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non–small-cell lung cancer who have been pre-treated with EGFR–tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. Methods From April 2015 to November 2016, we included 119 patients with advanced EGFR -mutated non–small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. Results T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1–12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number ( p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89–5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. Conclusion Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.

Abnormal lung function (abLF) at any age is a predictor of premature death. We aimed to determine the prevalence of abLF in different age groups (from infancy to elderly) and to investigate in the general population if associated risk factors (RFs) differ by age. Data was obtained from the LEAD Study, an observational, population-based cohort study. From 2012-2016 a random sample (stratified by age and gender) of 11.423 male and female, aged 6-80 years has been included. AbLF was defined as FEV1 The prevalence of abLF was 7.3% in male vs 6.0% in female in the youngest age group (6-15 yrs) and 9.9% in male vs 7.0% in female in the oldest one (60+ years), being always higher in males in all age groups. RFs associated with abLF varied across age groups (Table 1), except for doctor’s diagnosed asthma and low fat free mass index which were significant associated to abLF in all age groups. AbLF is substantially prevalent from childhood to older age and associated RFs vary with age. Therefore, abLF should be diagnosed as early as possible and appropriate actions should be implemented for modifiable RFs.

Background: The Lung, hEart, sociAl, boDy (LEAD) Study (ClinicalTrials.gov; NCT01727518; http://clinicaltrials.gov) is a longitudinal, observational, population-based Austrian cohort that aims to investigate the relationship between genetic, environmental, social, developmental and ageing factors influencing respiratory health and comorbidities through life. The general working hypothesis of LEAD is the interaction of these genetic, environmental and socioeconomic factors influences lung development and ageing, the risk of occurrence of several non-communicable diseases (respiratory, cardiovascular, metabolic and neurologic), as well as their phenotypic (ie, clinical) presentation.Methods: LEAD invited from 2011-2016 a random sample (stratified by age, gender, residential area) of Vienna inhabitants (urban cohort) and all the inhabitants of six villages from Lower Austria (rural cohort). Participants will be followed-up every four years. A number of investigations and measurements were obtained in each of the four domains of the study (Lung, hEart, sociAl, boDy) including data to screen for lung, cardiovascular and metabolic diseases, osteoporosis, and cognitive function. Blood and urine samples are stored in a biobank for future investigations.Results: A total of 11.423 males (47.6%) and females (52.4%), aged 6-80 years have been included in the cohort. Compared to governmental statistics, the external validity of LEAD with respect to age, gender, citizenship, and smoking status was high.Conclusions: In conclusion, the LEAD cohort has been established following high quality standards; it is representative of the Austrian population and offers a platform to understand lung development and ageing as a key mechanism of human health both in early and late adulthood.

Lessons Learned Conventional medicine and homeopathy work well together. Quality of life improves with additive homeopathy in patients with non-small cell lung cancer (NSCLC). Survival improves with additive homeopathy in patients with NSCLC. Background Patients with advanced non-small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of the present study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in patients with NSCLC. Methods In this prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter, phase III study, we evaluated the possible effects of additive homeopathic treatment compared with placebo in patients with stage IV NSCLC, with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the outpatients' centers every 9 weeks: 150 patients with stage IV NSCLC were included in the study; 98 received either individualized homeopathic remedies (n = 51) or placebo (n = 47) in a double-blinded fashion; and 52 control patients without any homeopathic treatment were observed for survival only. The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable Good Manufacturing Practice grade formulations. Results QoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p < .001). Median survival time was significantly longer in the homeopathy group (435 days) versus placebo (257 days; p = .010) as well as versus control (228 days; p < .001). Survival rate in the homeopathy group differed significantly from placebo (p = .020) and from control (p < .001). Conclusion QoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumor entities are warranted.

Matthias Helmut Urban,1 Philipp Eickhoff,2 Georg-Christian Funk,1 Otto Chris Burghuber,1 Michael Wolzt,3 Arschang Valipour1 1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria; 2Department of Obstetrics and Gynecology, St. Josef Hospital, Vienna, Austria; 3Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. Methods: The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. Results: Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. Conclusion: B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels. Keywords: cardiovascular risk, chronic obstructive pulmonary disease, comorbidity, subclinical atherosclerosis, biomarker

In the setting of pseudo-progression in a cancer patient who receives immunotherapeutic treatment, discontinuation of therapy is recommended if the patient is symptomatic. Here, we present two patients with advanced adenocarcinoma of the lung who developed massive tumor growth after initiation of treatment with the anti-PD-1 antibody pembrolizumab. Even though clinical deterioration occurred in the form of severe dyspnea and weight loss, pembrolizumab therapy was continued, as the speed of tumor growth suggested pseudo-progression and the tumors showed marked PD-L1 expression. This approach was successful, and both patients experienced impressive treatment responses within a few weeks.

With the ERS 10 Principles for Lung Health, @ERSTalk proposes a call to action to improve respiratory health and invites all stakeholders (politicians, policy makers, patients and the public) to support ithttp://ow.ly/9dW730mkhZu

Background: Impaired left ventricular diastolic function is common in patients with chronic obstructive pulmonary disease (COPD). Among several potential mechanisms dynamic hyperinflation might affect left ventricular filling through mechanical constraint on the heart and right to left ventricular interaction. Aims: We aimed to investigate the isolated effects of induced dynamic hyperinflation on left ventricular filling in healthy males in order to exclude other potential mechanisms. Methods: In a randomized cross-over interventional study we induced dynamic hyperinflation by the novel method Expiratory Stenosis Breathing (ESB) combining tachypnea and expiratory stenosis in healthy males (n=14). Dynamic hyperinflation was verified by intrinsic positive end-expiratory pressure (PEEPi). The effects on diastolic filling were measured by echocardiographic assessment of E/A-ratio and E/e9-ratio. Results: During ESB peak A-velocity increased and E/A-ratio adjusted for heart rate 60/min decreased from 1,90 (1,66 to 2,14) during spontaneous breathing (SB) to 1,63 (1,49 to 1,77) during maximum ESB (p=0,009). Septal E/e9-ratio increased from 6,2 (5,7 to 6,8) during SB to 7,1 (6,2 to 8,0) during maximum ESB (p=0,023). Higher PEEPi was correlated with lower E/A-ratio (p=0,001). Conclusions: Dynamic hyperinflation altered left ventricular filling in healthy males through increases in late diastolic filling during atrial systole and left ventricular filling pressure. This could be the result of increased constraint on the heart by the hyperinflated lungs. Our observations underline the role of dynamic hyperinflation as a determinant of left ventricular filling in patients with COPD.

Mid-term evaluation of the 2012–2018 European Respiratory Society strategy implementation http://ow.ly/WKhxk

Lung volume reduction surgery has been shown to be effective in patients with heterogeneous emphysema, but is also associated with a relatively high perioperative morbidity and mortality. Accordingly, several novel and potentially less invasive methods for bronchoscopic lung volume reduction have been developed. Endobronchial valve (EBV) therapy is one such therapeutic approach in patients with advanced emphysema. It has been the most widely studied technique over the past years and represents an effective treatment option for patients with severe heterogeneous upper- or lower-lobe-predominant emphysema. The choice of EBV therapy largely depends on the distribution of emphysema and the presence or absence of interlobar collateral ventilation. Adequate patient selection and technical success of valve implantation with the intention of lobar exclusion are predictive factors for positive outcomes. This review attempts to highlight the milestones in the development of bronchoscopic lung volume reduction with one-way valve implantation over the past few years.

Chronic obstructive pulmonary disease (COPD) represents a major global health problem; however, there are no data regarding clinical phenotypes of these patients in Austria. 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 (FEV1/FVC) ratio

Background: COPD is associated with an excess atherosclerotic risk. Both, COPD and atherosclerosis are mediated by systemic inflammation. Roflumilast, as an anti-inflammatory drug, revealed potential atheroprotective effects in patients with COPD. Aims: To investigate the effects of Roflumilast on subclinical atherosclerosis (i.e. arterial stiffness, endothelial dysfunction) and a potential association with systemic inflammation in COPD. Methods: 80 COPD patients were randomized to receive Roflumilast or placebo for 24 weeks. Arterial stiffness was measured by pulse wave velocity (PWV) and augmentation index (AIx). Endothelial dysfunction was assessed via reactive hyperemia index (RHI), circulating levels of asymmetric dimethylarginine (ADMA) and matrix metalloproteinase-9 (MMP-9). Systemic inflammation was quantified by C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Results: 67 patients completed the study, 33 of which received Roflumilast and 34 received placebo. The primary endpoint, change from baseline PWV, did not show a significant difference between Roflumilast and placebo (1.07 [95% CI 0.98 – 1.17] vs. 0.99 [95% CI 0.91 – 1.08], p = 0.214). Roflumilast did not improve AIx or markers of endothelial dysfunction (RHI, ADMA, MMP-9) and systemic inflammation (CRP, IL-6, TNF-alpha). We observed a significant improvement of 6-minute walking test with Roflumilast compared to placebo (59.2 [95% CI 18.3 – 100] vs. 0.69 [95% CI -39.7 – 42.1], p = 0.045). Conclusions: Our study does not support an atheroprotective effect of Roflumilast. However, there might be an improvement of exercise capacity with Roflumilast in patients with COPD.

Task forces use rigorous methodology, and the ERS will not tolerate interference with the processes by outsiders http://ow.ly/WwIe30cyhDO

Background Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients’ health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients’ and physicians’ reasons leading to clinical decisions on MT. Methods Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients’ and physicians’ reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models. Results Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p

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.

Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function.We conducted a longitudinal pilot study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Eighteen non-smoking patients with stable moderate-to-severe COPD [67 % male; median (first to third quartiles) Forced Expiratory Volume in 1 second (FEV1) % predicted: 38 % (28-55 %); body mass index: 26 kg/m(2) (24-28 kg/m(2))] free from cardiovascular risk factors were evaluated. Systemic vascular function was assessed by means of flow-mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after 12 months.Flow-mediated dilation significantly decreased from 13.5 % (11-15 %) at baseline to 9.8 % (6-12 %; p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations and HOMA-IR increased from 94 mg/dl (86-103 mg/dl) to 102 mg/dl (94-111 mg/dl; p = 0.027) and from 1.2 (0.8-2.1) to 1.7 (1.2-3.0; p = 0.023), respectively. There was a significant relationship between changes in endothelial function and changes in fasting serum glucose (r = - 0.483, p = 0.009), HOMA-IR (r = - 0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05).Altered glucose metabolism may be associated with progression of endothelial dysfunction in patients with COPD.

Mit dem National Lung Screening Trial (NLST) konnte erstmals in einer prospektiven randomisierten Studie gezeigt werden, dass durch ein Screening mit einer Niedrigdosis (low dose) CT (LD-CT) die Mortalitat des Lungenkarzinoms gesenkt werden kann. Derzeit sind noch viele Fragen offen, wie diese Ergebnisse auf Osterreich ubertragen werden konnen. Insbesondere betrifft dies die Definition des Personenkreises, fur den ein erhohtes Lungenkrebsrisiko vorliegt, und den Umgang mit den vielen zu erwartenden falsch positiven Befunden. Daher wird eine Untersuchung einer Person zur Fruherkennung eines Lungenkarzinoms nur unter Beachtung der Richtlinien der zwei Fachgesellschaften empfohlen. Es sollen nur Personen mit einem deutlich erhohten Lungenkarzinomrisiko untersucht werden (Alter > 55 Jahre, 30 pack-years Raucheranamnese, aktive Raucher oder Exraucher seit < 15 Jahren). Die zu screenenden Personen mussen uber die hohe Wahrscheinlichkeit von falsch-positiven Screening-Ergebnissen und die zur weiteren Abklarung notwendigen Folgeuntersuchungen und moglichen invasiven Eingriffe informiert werden. Die Patienten mussen daruber informiert werden, dass ein LD-CT Screening sie nicht sicher vor dem Auftreten eines inoperablen Lungenkarzinoms schutzt. Die CT-Untersuchungen sollen in Low dose CT Technik uber mindestens 3 Jahre in jahrlichen Intervallen durchgefuhrt werden. Die Abklarung gefundener Rundherde muss in standardisierter Weise erfolgen um zu gewahrleisten, dass bei der gegebenen hohen Wahrscheinlichkeit fur falsch positive Rundherde die weiterfuhrende Abklarung zielgerichtet erfolgt.

Prolonged alveolar-pleural air leaks are associated with increased morbidity and mortality. Endoscopic valve therapy has been recently introduced as a potential less invasive treatment option. We aimed at quantifying the effects of valve therapy on air leak flow and clinical outcomes in patients with prolonged air leaks.We report on a series of 16 patients with high comorbidity and evidence of continuous air leak flow in whom chest tubes remained in place for at least 7 days. After identification of the source of the air leak by use of the balloon occlusion technique, endobronchial one-way valves were implanted. Digital chest tube monitoring was used to assess air leak flow before, during, and after valve implantation until chest tube removal.The source of the air leak was endoscopically identified in 13 patients (81%). After valve implantation, air leak flow decreased significantly from 871±551 mL/min to 61±72 mL/min immediately after the intervention (p0.001). The mean duration of chest tube drainage was 18±8 days before and 9±6 days after the intervention (p0.01). Ten patients were considered responders, and 3 patients were nonresponders. Responders demonstrated consistent air leak flow levels below 100 mL/min until chest tube removal. Long-term follow-up was available for 9 patients. No adverse events related to the valve implants were reported at follow-up. Seven patients underwent valve removal without any further complications.Endoscopic implantation of one-way valves leads to a significant reduction in air leakage flow and may thus be a valuable treatment option in patients with prolonged air leakage.

In patients with non-small-cell lung cancer, the presence of brain metastases requires specific treatment due to the unfavourable overall impact of these lesions. Treatment with the tyrosine kinase inhibitor afatinib was shown to induce complete and long-lasting remissions in the five patients described here. All of them had multiple brain lesions and presented with symptoms. Study evidence suggests beneficial effects of afatinib in this respect, underlining these clinical observations. Afatinib might be incorporated into current treatment algorithms, allowing for the omission of radiotherapy, provided that larger phase III trials confirm the potential of epidermal growth factor receptor tyrosine kinase inhibitors in this respect.

The epidemiology of chronic obstructive pulmonary disease (COPD) in critically ill patients is largely unknown. The aims of the study were: 1) to determine whether COPD, either as the cause of intensive care unit (ICU) admission or as a comorbid condition, is an independent risk factor for increased morbidity and mortality; and 2) to investigate time trends in proportion and outcome of acute respiratory failure in patients with COPD admitted to ICUs. Prospectively recorded data from 194 453 adults consecutively admitted to 87 Austrian ICUs over a period of 11 years (1998-2008) were retrospectively analysed. COPD was present in 8.6% of all patients. The risk-adjusted mortality of patients with COPD was higher than in patients without COPD. The presence of COPD was an independent risk factor for increased mortality and was associated with prolonged mechanical ventilation and prolonged weaning. During the course of the 11 years, the proportion of acute respiratory failure due to COPD increased by about two-thirds, and the use of noninvasive ventilation within the COPD cohort more than doubled. Simultaneously, the risk-adjusted mortality of patients with COPD improved. In critically ill patients, the presence of COPD is increasing and is an independent risk factor for mortality and morbidity.