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1.
Exp Physiol ; 106(2): 532-543, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33174314

RESUMO

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.


Assuntos
Pulmão/fisiologia , Respiração , Adulto , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Capacidade Inspiratória , Masculino , Adulto Jovem
2.
Respirology ; 26(2): 153-160, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32725799

RESUMO

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.


Assuntos
Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Rigidez Vascular , Idoso , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacologia , Benzamidas/efeitos adversos , Benzamidas/farmacologia , Biomarcadores/metabolismo , Ciclopropanos/efeitos adversos , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Feminino , Seguimentos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos
3.
Eur Respir J ; 55(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32060069

RESUMO

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 (p<0.05) associated with high blood eosinophil counts (binary multivariable logistic regression analysis), and had an additive effect; and 2) after excluding these factors, in those older than 18 years, blood eosinophil counts were higher in males than in females (median 120 (5%-95% CI: 30-330) versus 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.


Assuntos
Asma/epidemiologia , Eosinofilia/epidemiologia , Eosinófilos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/sangue , Áustria/epidemiologia , Criança , Comorbidade , Estudos Transversais , Demografia , Eosinofilia/sangue , Feminino , Humanos , Contagem de Leucócitos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença Pulmonar Obstrutiva Crônica/sangue , Adulto Jovem
4.
Anticancer Drugs ; 30(7): e0787, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31305295

RESUMO

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.


Assuntos
Quinase do Linfoma Anaplásico/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbazóis/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organofosforados/administração & dosagem , Piperidinas/administração & dosagem , Prognóstico , Pirimidinas/administração & dosagem , Sulfonas/administração & dosagem , Taxa de Sobrevida
5.
J Epidemiol ; 29(8): 315-324, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30344197

RESUMO

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.


Assuntos
Estudos de Coortes , Doenças não Transmissíveis/epidemiologia , Doenças Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria/epidemiologia , Criança , Comorbidade , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
6.
Front Psychol ; 14: 1115832, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936013

RESUMO

While research on possible adaptive processes in language history has recently centered mostly on phonological variables, here, I return the focus on the lexicon in two different ways. First, I take up the familiar theme of the responsiveness of language structure to the local conditions at different elevations of the earth's surface by exploring further the idea that language communities at high altitudes may tend not to distinguish lexically, as, e.g., English does, between "cloud" and "fog." Analyses of a global dataset of languages as well as in-depth study of the languages of the Central Andes are consistent in showing a wide spread of colexification of "cloud" and "fog" across elevations, whereas distinguishing languages tend more to be spoken at lower elevations. Statistically, there is global support for the idea that colexification is triggered by high elevation, but a closer look, in particular at the Andean dataset, paints a more nuanced picture. Concretely, it shows that in some language families, there are consistent preferences for either colexifying or distinguishing between "cloud" and "fog." In particular, the behavior of the large Quechuan family, which ranges across high- and low-elevation environments but still is consistently colexifying, shows no evidence for adaptive processes within language families. This result is open to various interpretations and explanations, for they suggest lineage-specific preferences for or against colexification that run counter to global trends. It is also at odds with the notions of "efficient communication" and "communicative need" as far as they relate to lexical categories and bars mechanistic or deterministic views on the processes in which the categories of languages are molded.

7.
Wien Klin Wochenschr ; 135(1-2): 35-44, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36044093

RESUMO

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with reduced exercise capacity. In COPD iron deficiency is found in up to 50% of patients and may impair exercise capacity, the potential therapeutic effect is yet unknown. We aimed to estimate the beneficial effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD. METHODS: In this non-randomized, interrupted time series pilot trial we enrolled outpatients with stable COPD (GOLD II and III) and nonanemic iron deficiency (i.e., ferritin level < 100 µg/l or ferritin level 100-300 µg/l if transferrin saturation < 20%). Patients with cardiovascular-or inflammatory diseases were excluded. Participants performed 6­minute walking test (6-MWT) and cardiopulmonary exercise testing (CPET) and completed the St. George's Respiratory Questionnaire (SGRQ). RESULTS: From 35 screened patients, 11 (72% male, 63 ± 8 years, FEV1%predicted 44 ± 14) were included. Mean ferritin and hemoglobin were 70 ± 41 µg/l and 13.8 ± 1.7 g/dl, respectively. Four weeks after iron administration the 6­MWT distance increased by 34.7 ± 34.4 m (95% CI, 10.0-59.3); p = 0.011. The VO2max increased by 1.87 ± 1.2 ml/kg/min (95% CI, 0.76-3); p = 0.006. Mean score of SGRQ was reduced by 7.56 ± 6.12 units (95% CI, 3 to 11); p = 0.004. The insignificant alteration in hemoglobin did not correlate with increase in exercise capacity. CONCLUSION: Administration of intravenous iron was associated with improved exercise capacity and quality of life in stable COPD patients independent of hemoglobin. Our data provide a basis to calculate a statistically sufficient sample size for a randomized controlled follow-up study.


Assuntos
Tolerância ao Exercício , Compostos Férricos , Deficiências de Ferro , Ferro , Maltose , Doença Pulmonar Obstrutiva Crônica , Feminino , Humanos , Masculino , Ferritinas/sangue , Seguimentos , Hemoglobinas , Ferro/uso terapêutico , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Pessoa de Meia-Idade , Idoso , Compostos Férricos/uso terapêutico , Maltose/uso terapêutico , Administração Intravenosa , Análise de Séries Temporais Interrompida
8.
Wien Klin Wochenschr ; 134(9-10): 399-419, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35449467

RESUMO

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV­2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV­2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV­2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients.


Assuntos
COVID-19 , Pneumopatias , Pneumologia , Áustria/epidemiologia , COVID-19/epidemiologia , Criança , Controle de Doenças Transmissíveis , Humanos , Pneumopatias/epidemiologia , Pneumopatias/terapia , SARS-CoV-2 , Adulto Jovem
9.
R Soc Open Sci ; 8(4): 202232, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33996125

RESUMO

This contribution theorizes the historical dynamics of so-called language isolates, languages which cannot be demonstrated to belong to any known language family. On the basis of a qualitative review of how isolates, language families or their branches lost territory to other languages through time, I develop a simple model for the genesis of isolates as a function of proximity to major geographical barriers, and pit it against an alternative view that sees them as one manifestation of linguistic diversity generally. Using a variety of statistical techniques, I test both accounts quantitatively against a worldwide dataset of language locations and distances to geographical barriers, and find support for the position that views language isolates as one manifestation of linguistic diversity generally. However, I caution that different processes which are not necessarily mutually exclusive may have shaped the present-day distribution of language isolates. These may form elements of a broader theory of language isolates in particular and language diversity in general.

10.
PLoS One ; 16(2): e0245522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33544750

RESUMO

The first decades of the 21st century have witnessed a renewed interest in the relationship between language structure and the various social and ecological niches in which the languages of the world are used and against the background of which they evolved. In this context, Everett (2013) argued for direct geographical influences on the sound structure of languages. It was observed that ejective consonants, produced with a sudden burst of non-pulmonic air to a salient acoustic effect, tend to occur in high-altitude environments in which these sounds may be adaptive due to a reduced articulatory effort and/or to prevent desiccation. Here, we evaluate this claim and at the same time place it into a broader context. We observe that the distribution of another class of typologically unusual sounds, uvulars, is highly similar to that of ejectives, but that the proposed explanations are not available to account for the similar geographical patterning of uvulars. Hence, we test an alternative explanatory account that would posit indirect rather than direct environmental influences on language structure that are mediated by anthropological factors, in particular the relative sociolinguistic isolation of speech communities at the highest altitudes. Applying Bayesian Logistic Mixed Effects Regression to a large database of phonological inventories of the world's languages, however, we do not find strong support for either a correlation of ejectives or uvulars with high-altitude environments, though the association is somewhat stronger for ejectives than uvulars. A phylogenetic exploration of the development of both classes of sounds in two large language families spoken in widely different environments, Indo-European and Sino-Tibetan, together with a qualitative assessment of the dedicated literature, in contrast, suggests a strong role of language contact rather than environmental factors.


Assuntos
Altitude , Idioma , Fonética , Som , Acústica da Fala , Geografia , Humanos
11.
J Clin Med ; 11(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35011794

RESUMO

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition with constantly increasing mortality rates. Interleukin (IL)-33 and its decoy receptor, soluble suppression of tumorigenicity 2 (sST2), play a central role in the inflammatory response during infection. sST2 was suggested as a factor in the pathogenesis of COPD and emerged as a predictor of mortality in other non-communicable diseases. The role of sST2 as a predictor of mortality remains unclear in COPD yet. In this cohort study, we measured circulating concentrations of IL-33 and sST2 in the serum of patients with stable COPD (n = 59), patients with acute exacerbation of COPD (n = 29) and smoking (n = 20) and non-smoking controls (n = 20), using commercially available ELISAs, and investigated the prognostic role of sST2 in stable COPD. sST2 levels were significantly higher in COPD patients and smokers compared with non-smoking controls. We identified systolic blood pressure, forced expiratory volume in 1 s (FEV1% predicted), neutrophil count, lactate dehydrogenase and pack-years index as independent predictors of sST2 levels. During a median follow-up time of 10.6 years, 28 patients (47.5%) died. sST2 was an independent predictor of all-cause mortality in patients with COPD with a hazard ratio of 2.9 (95% CI 1.1-8.4, p = 0.035) per one standard deviation after adjustment for age, sex, pack-years, FEV1% predicted and C-reactive protein (CRP). sST2 concentrations are associated with severity of disease and long-term outcome in patients with COPD.

12.
Front Med (Lausanne) ; 8: 791410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047532

RESUMO

Background and Objectives: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for cardiovascular disease. This study aimed to investigate the relationship between pulmonary hyperinflation and baroreceptor reflex sensitivity (BRS), a surrogate for cardiovascular risk. Methods: 33 patients with COPD, free from clinical cardiovascular disease, and 12 healthy controls were studied. Participants underwent pulmonary function and non-invasive hemodynamic measurements. BRS was evaluated using the sequence method during resting conditions and mental arithmetic stress testing. Results: Patients with COPD had evidence of airflow obstruction [forced expiratory volume in 1 s predicted (FEV1%) 26.5 (23.3-29.1) vs. 91.5 (82.8-100.8); P < 0.001; geometric means (GM) with 95% confidence interval (CI)] and lung hyperinflation [residual volume/total lung capacity (RV/TLC) 67.7 (64.3-71.3) vs. 41.0 (38.8-44.3); P < 0.001; GM with 95% CI] compared to controls. Spontaneous mean BRS (BRSmean) was significantly lower in COPD, both during rest [5.6 (4.2-6.9) vs. 12.0 (9.1-17.6); P = 0.003; GM with 95% CI] and stress testing [4.4 (3.7-5.3) vs. 9.6 (7.7-12.2); P < 0.001; GM with 95% CI]. Stroke volume (SV) was significantly lower in the patient group [-21.0 ml (-29.4 to -12.6); P < 0.001; difference of the means with 95% CI]. RV/TLC was found to be a predictor of BRS and SV (P < 0.05 for both), independent of resting heart rate. Conclusion: We herewith provide evidence of impaired BRS in patients with COPD. Hyperinflation may influence BRS through alteration of mechanosensitive vagal nerve activity.

13.
Front Med (Lausanne) ; 8: 659108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017848

RESUMO

Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD. Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects (n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEPi) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio. Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49-1.77] vs. 1.85 [0.95-2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = -0.007, p = 0.001). Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD.

14.
PLoS One ; 16(3): e0249192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780476

RESUMO

Label-free and gentle separation of cell stages with desired target properties from mixed stage populations are a major research task in modern biotechnological cultivation process and optimization of micro algae. The reported microfluidic sorter system (MSS) allows the subsequent investigation of separated subpopulations. The implementation of a viability preserving MSS is shown for separation of late stage 1 Haematococcus pluvialis (HP) cells form a mixed stage population. The MSS combines a three-step flow focusing unit for aligning the cells in single file transportation mode at the center of the microfluidic channel with a pure hydrodynamic sorter structure for cell sorting. Lateral displacement of the cells into one of the two outlet channels is generated by piezo-actuated pump chambers. In-line decision making for sorting is based on a user-definable set of image features and properties. The reported MSS significantly increased the purity of target cells in the sorted population (94%) in comparison to the initial mixed stage population (19%).


Assuntos
Separação Celular/instrumentação , Clorofíceas/citologia , Dispositivos Lab-On-A-Chip
15.
Pharmaceuticals (Basel) ; 13(11)2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171712

RESUMO

In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement-positive non-small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive patients were considered responders. Median overall survival from lorlatinib initiation was 10.2 and 20.0 months for the ALK- and ROS1-positive groups, respectively. In the ALK-positive group, lorlatinib proved efficacy after both brigatinib and alectinib. Lorlatinib treatment was well tolerated. Later-line lorlatinib treatment can induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer.

16.
Wien Klin Wochenschr ; 132(13-14): 365-386, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32533443

RESUMO

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-CoV­2 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.


Assuntos
Infecções por Coronavirus , Coronavirus , Pneumopatias/complicações , Pandemias , Pneumonia Viral , Pneumologia , Adolescente , Adulto , Áustria , Betacoronavirus , COVID-19 , Criança , Doença Crônica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Humanos , Pneumopatias/terapia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , SARS-CoV-2
17.
Wien Klin Wochenschr ; 130(7-8): 238-246, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29372409

RESUMO

BACKGROUND: Screening for lung cancer with a low-dose computed tomography (CT) scan is estimated to prevent 3 deaths per 1000 individuals at high risk; however, false positive results and radiation exposure are relevant harms and deserve careful consideration. Screening candidates can only make an autonomous decision if doctors correctly inform them of the pros and cons of the method; therefore, this study aimed to evaluate whether doctors understand the test characteristics of lung cancer screening. METHODS: In a randomized trial 556 doctors (members of the Austrian Respiratory Society) were invited to answer questions regarding lung cancer screening based on online case vignettes. Half of the participants were randomized to the group 'solutions provided' and received the correct solutions in advance. The group 'solutions withheld' had to rely on prior knowledge or estimates. The primary endpoint was the between-group difference in the estimated number of deaths preventable by screening. Secondary endpoints were the between-group differences in the prevalence of lung cancer, prevalence of a positive screening results, sensitivity, specificity, positive predictive value, and false negative rate. Estimations were also compared with current data from the literature. RESULTS: The response rate was 29% in both groups. The reduction in the number of deaths due to screening was overestimated six-fold (95% confidence interval CI: 4-8) compared with the actual data, and there was no effect of group allocation. Providing the correct solutions to doctors had no systematic effect on their answers. CONCLUSION: Doctors poorly understand the test characteristics of lung cancer screening. Providing the correct solutions in advance did not improve the answers. Continuing education regarding lung cancer screening and the interpretation of test characteristics may be a simple remedy. CLINICAL TRIAL REGISTRATION: Clinical trial registered with www.clinicaltrials.gov (NCT02542332).


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Programas de Rastreamento , Áustria , Humanos , Neoplasias Pulmonares/diagnóstico , Distribuição Aleatória , Tomografia Computadorizada por Raios X
18.
Wien Klin Wochenschr ; 130(19-20): 561-568, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30066095

RESUMO

BACKGROUND: Non-invasive ventilation (NIV) is used to treat acute hypercapnic respiratory failure (AHRF) in patients with chronic obstructive pulmonary disease (COPD); however, long-term outcomes following discharge are largely unknown. This study aimed to characterize long-term outcomes and identify associated markers in patients with COPD after surviving the first episode of HRF requiring NIV. METHODS: This study retrospectively analyzed 122 patients, mean age 62 ± 8 years, 52% female and forced expiratory volume in 1 s (FEV1) predicted 30 ± 13%, admitted with an acute hypercapnic exacerbation of COPD and receiving a first-ever NIV treatment between 2000 and 2012. RESULTS: A total of 40% of the patients required hospital readmission due to respiratory reasons within 1 year. Persistent hypercapnia leading to the prescription of domiciliary NIV, older age and lower body mass index (BMI) were risk factors for readmission due to respiratory reasons. Survival rates were 79% and 63% at 1 and 2 years after discharge, respectively. A shorter time to readmission and recurrent hypercapnic failure, lower BMI and acidemia on the first admission, as well as hypercapnia at hospital discharge were correlated with a decreased long-term survival. CONCLUSION: Patients with COPD surviving their first episode of AHRF requiring NIV are at high risk for readmission and death. Severe respiratory acidosis, chronic respiratory failure and a lower BMI imply shorter long-term survival.


Assuntos
Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Idoso , Feminino , Humanos , Hipercapnia , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/terapia , Estudos Retrospectivos
19.
Artigo em Inglês | MEDLINE | ID: mdl-28115840

RESUMO

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.


Assuntos
Arginina/análogos & derivados , Aterosclerose/diagnóstico por imagem , Artéria Braquial/diagnóstico por imagem , Inflamação/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Idoso , Arginina/sangue , Doenças Assintomáticas , Aterosclerose/sangue , Aterosclerose/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Mediadores da Inflamação/sangue , Modelos Lineares , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Espirometria , Ultrassonografia
20.
BMJ Open ; 5(6): e006510, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-26044757

RESUMO

OBJECTIVE: Recent observations revealed substantial differences in smoking behaviour according to individuals' migration background. However, smoking cessation strategies are rarely tailored on the basis of a migration background. We aimed to determine whether smoking behaviour and preferences for smoking cessation programmes differ between Austrian migrant smokers and Austrian smokers without a migration background. STUDY DESIGN: Cross-sectional study. SETTING: Recruitment and interview were performed at public places in Vienna, Austria. PARTICIPANTS: The 420 smokers included: 140 Bosnian, 140 Turkish migrant smokers of the first or second generation, as well as 140 Austrian smokers without a migration background. METHODS: We cross-sectionally assessed determinants of smoking behaviour and smoking cessation of every participant with a standardised questionnaire. PRIMARY OUTCOME MEASURE: The Fagerström Test for Nicotine Dependence. SECONDARY OUTCOME MEASURES: Determinants of smoking behaviour, willingness to quit smoking and smoking cessation. RESULTS: Nicotine addiction expressed via the Fagerström score was significantly higher in smokers with a migration background versus those without (Bosnian migrant smokers 4.7 ± 2.5, Turkish migrant smokers 4.0 ± 2.0, Austrian smokers without a migration background 3.4 ± 2.3, p<0.0001). Bosnian and Turkish migrant smokers described a greater willingness to quit, but have had more previous cessation trials than Austrian smokers without a migration background, indicating an increased demand for cessation strategies in these study groups. They also participated in counselling programmes less often than Austrian smokers without a migration background. Finally, we found significant differences in preferences regarding smoking cessation programmes (ie, preferred location, service offered in another language besides German, and group rather than single counselling). CONCLUSIONS: We found significant differences in addictive behaviour and cessation patterns between smokers with and without a migration background. Our results indicate a strong demand for adjusting cessation programmes to the cultural background.


Assuntos
Aconselhamento , Emigração e Imigração , Aceitação pelo Paciente de Cuidados de Saúde , Abandono do Hábito de Fumar/etnologia , Tabagismo/etnologia , Migrantes , Adulto , Áustria/etnologia , Comportamento Aditivo , Bósnia e Herzegóvina/etnologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/etnologia , Inquéritos e Questionários , Nicotiana , Turquia/etnologia , Adulto Jovem
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