Background
Airway structural changes are important in asthma pathology and require further investigations.
Objective
We sought to evaluate which computed tomography (CT) indices, bronchial ...histological traits, or blood and bronchoalveolar lavage (BAL) biomarkers correlate best with lung function abnormalities in asthma.
Methods
In 105 white adult asthmatics (53 with a component of fixed airflow obstruction), we determined airway cross‐sectional geometry of two proximal (the right upper lobe apical segmental and the left apicoposterior) and two distal (the right and the left basal posterior) bronchi, quantified the low‐attenuation lung area (LAA%), and analysed clusters based on airway CT‐metrics. We also performed bronchofiberoscopy with BAL and endobronchial biopsy, assessed blood and BAL biomarkers, including interleukin (IL)‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐17A, IL‐23, interferon (INF)γ and periostin, together with circulating a disintegrin and metalloproteinase domain‐containing protein (ADAM)33, and investigated interplays between analysed variables.
Results
Patients with fixed airflow limitation were characterized by lower lumen area and increased wall area and wall thickness ratios in distal airways, accompanied by raised LAA%. They had also higher blood neutrophilia, blood and BAL eosinophilia, increased circulating fibrinogen, periostin, and ADAM33. Blood neutrophilia, serum high density lipoproteins, thyroid‐stimulating hormone, and shortened activated partial thromboplastin time were determinants of thicker reticular basement membrane (RBM). BAL eosinophilia was the only positive predictor of collagen I accumulation. Surprisingly, we observed a negative correlation between RBM thickening and collagen I deposit. Cluster analysis based on CT‐metrics of the right lower lobe basal posterior bronchus revealed three well‐separated clusters similar in age, asthma duration, and BMI, but different in RBM thickness, collagen I accumulation, and inflammatory markers.
Conclusions and clinical relevance
Airway remodelling traits are mainly related to the Th2 profile, higher circulating ADAM33, and blood neutrophilia. Lung function abnormalities and RBM thickening correlate better with CT‐metrics of distal than proximal airways.
In this contribution there are considered interval‐valued methods of improving the quality of classification by the
k‐
N
N binary classifiers in the case of large number of attributes in data sets. ...One of the possible applications of the introduced method are the microarray data so the presented results may be applied in medical diagnosis support, for example, in identification of marker genes. The proposed algorithm involving reduction methods of time complexity and interval modeling of data using interval‐valued aggregation functions has a significantly higher classification quality than the other considered algorithm with the aggregation method involving the numerical arithmetic mean. The former algorithm is based on the interval‐valued aggregation of uncertainty intervals determined on the basis of certainty coefficients of individual
k‐
N
N classifiers while the latter is based on the aggregation of certainty coefficients of individual
k‐
N
N classifiers with the use of the numerical arithmetic mean. Moreover, the performance of the new algorithm based on interval‐valued methods was compared with the known from the literature classifiers in cancer diagnosis based on gene expression microarrays. The obtained results prove that in practical applications the newly proposed algorithm can be successfully used.
The aim of this study is to apply and evaluate the usefulness of the hybrid classifier to predict the presence of serious coronary artery disease based on clinical data and 24-hour Holter ECG ...monitoring. Our approach relies on an ensemble classifier applying the distributivity equation aggregating base classifiers accordingly. Such a method may be helpful for physicians in the management of patients with coronary artery disease, in particular in the face of limited access to invasive diagnostic tests, i.e., coronary angiography, or in the case of contraindications to its performance. The paper includes results of experiments performed on medical data obtained from the Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland. The data set contains clinical data, data from Holter ECG (24-hour ECG monitoring), and coronary angiography. A leave-one-out cross-validation technique is used for the performance evaluation of the classifiers on a data set using the WEKA (Waikato Environment for Knowledge Analysis) tool. We present the results of comparing our hybrid algorithm created from aggregation with the distributive equation of selected classification algorithms (multilayer perceptron network, support vector machine,
-nearest neighbors, naïve Bayes, and random forests) with themselves on raw data.
Human rhinoviruses (HRV) are frequent cause of asthma exacerbations, however the influence of airway inflammation on the severity of viral infection is poorly understood. Here, we investigated how ...cytokine-induced remodeling of airway epithelium modulates antiviral response. We analyzed gene expression response in in vitro differentiated bronchial epithelium exposed to cytokines and next infected with HRV16. IL-13-induced mucous cell metaplasia (MCM) was associated with impaired ciliogenesis and induction of antiviral genes, resulting in lower susceptibility to HRV. Epithelial-mesenchymal transition caused by TGF-β was associated with increased virus replication and boosted innate response. Moreover, HRV infection per se caused transient upregulation of MCM markers and growth factors, followed by low-level virus replication and shedding. Our data suggest that the outcome of HRV infection depends on the type of lower airway inflammation and the extent of epithelial damage. Type-2 inflammation (eosinophilic asthma) may induce antiviral state of epithelium and decrease virus sensitivity, while growth factor exposure during epithelial repair may facilitate virus replication and inflammatory response. Additionally, responses to HRV were similar in cells obtained from asthma patients and control subjects, which implicates that antiviral mechanisms are not intrinsically impaired in asthma, but may develop in the presence of uncontrolled airway inflammation.
Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral ...anticoagulants (DOACs) in breast cancer women.
In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 interquartile range 56–69 years, CHA2DS2–VASc 2 2,3) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack TIA, venous thromboembolism VTE) and bleeding events (major and clinically relevant non-major bleeding CRNMB) were recorded in follow-up.
During a median follow-up of 40 (interquartile range 28–50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 29–33) vs. 26 24–29) kg/m2, p = 0.02) and CHA2DS2–VASc score (3 3) vs. 2 1–3), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 2.3%/year, rivaroxaban, n = 3 5.22%/ year, and dabigatran, n = 2 4%/ year). No death was related to bleeding.
This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy.
A•There have been no published studies on the use of direct oral anticoagulants in breast cancer patients receiving hormonal therapy.•In our study the frequency of unfavorable clinical events was similar to those reported in large clinical trials.•Direct oral anticoagulants are safe and effective in long-term therapy of breast cancer women with atrial fibrillation during adjuvant hormonal therapy.
Given increased risk of cardiovascular events in asthma we hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme involved in atherosclerosis, is associated with ...proinflammatory and prothrombotic blood alterations in this disease.
In 164 adult asthmatics (63 with severe asthma) we measured plasma Lp-PLA2 activity using the PLAC test. We determined its relations to inflammation and prothrombotic blood alterations.
In asthma, Lp-PLA2 was inversely related to the age (β = −0.1 −0.18 to −0.02) and was lower in women (n = 122 74%, 205 182–242 vs. 243 203–262 nmol/min/ml, p = 0.001). Interestingly, Lp-PLA2 correlated negatively with the asthma severity score (β = −0.15 −0.23 to −0.07), being 10.3% higher in those with non-severe (mild or moderate) asthma (n = 101, 62%) as compared to the severe disease subtype (224 191–261 vs. 203 181–229, p = 0.006 after adjustment for potential confounders). Lp-PLA2 activity was positively related to the levels of low-density lipoprotein (β = 0.1 0.02–0.18), triglycerides (β = 0.11 0.03–0.19) and glucose (β = 0.1 0.02–0.18) and inversely to the tumor necrosis factor α (β = −0.27 −0.35 to −0.2), high sensitivity C-reactive protein (β = −0.1 −0.19 to −0.02) and fibrinogen (β = −0.12 −0.21 to −0.03), as well as prothrombin (β = −0.16 −0.24 to −0.08), and parameters describing thrombin generation potential, such as endogenous thrombin potential (β = −0.14 −0.21 to −0.06) and peak thrombin generated (β = −0.2 −0.28 to −0.12).
Elevated Lp-PLA2 activity in non-severe asthmatics suggests increased atherosclerotic risk in this group. Lower Lp-PLA2 activity accompanied by its inverse relationship to inflammatory or prothrombotic blood biomarkers observed in turn in severe asthmatics might be related to the pathogenesis of more severe asthma phenotype.
Background
Emerging data indicates that extracellular traps (ETs), structures formed by various immune cell types, may contribute to the pathology of noninfectious inflammatory diseases. Histone ...hypercitrullination is an important step in ETs formation and citrullinated histone H3 (H3cit) is considered a novel and specific biomarker of that process. In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers.
Methods
In 60 white adult stable asthmatics and 50 well‐matched controls we measured serum levels of H3cit. In asthmatics we also performed bronchoscopy with BAL. We analyzed blood and BAL biomarkers, including interleukin (IL)‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐17A and interferon γ. For statistical analysis, Mann–Whitney U‐test, χ2 test, one‐way ANCOVA, ROC curve analysis and univariate linear regression were applied. Independent determinants of H3cit were established in a multiple linear regression model.
Results
Asthma was characterized by elevated circulating H3cit (17.49 11.25–22.58 vs. 13.66 8.66–18.87 ng/ml, p = 0.03). In asthmatics positive associations were demonstrated between serum H3cit and lung function variables, including total lung capacity (TLC) (β = 0.37 95% CI 0.24–0.50) and residual volume (β = 0.38 95% CI 0.25–0.51). H3cit was increased in asthma patients receiving systemic steroids (p = 0.02), as well as in subjects with BAL eosinophilia above 144 cells/ml (p = 0.02). In asthmatics, but not in controls, circulating H3cit correlated well with number of neutrophils (β = 0.31 95% CI 0.19–0.44) and monocytes (β = 0.42 95% CI 0.29–0.55) in peripheral blood. Furthermore, BAL macrophages, BAL neutrophils, TLC, high‐sensitivity C‐reactive protein, Il‐12p70 and bronchial obstruction degree were independent determinants of H3cit in a multivariate linear regression model.
Conclusions
Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs formation. Inhibition of ETs might be a therapeutic option in selected asthma phenotypes, such as neutrophilic asthma.
Background
Almond allergy is common and can manifest in two different forms. Primary almond allergy has been reported to be associated with sensitization to almond legumin Pru du 6. In birchendemic ...regions, there is a link between birch‐pollinosis which is likely based on a cross‐reactive Bet v 1 homologue, a yet unidentified allergen in almond. Therefore, we sought to identify and characterize a Bet v 1‐homologue in almond.
Methods
The expression of a Bet v 1 homologue in almond kernels was confirmed by mass spectrometry. The recombinant protein was produced in Escherichia coli and its cross‐reactivity and allergenic potency was analyzed by IgE quantitative and competitive ELISA, immunoblotting and basophil histamine release using sera from 17 almond allergic patients.
Results
The identified Bet v 1 homologue received the designation Pru du 1.0101. Pru du 1.0101 bound IgE from 82 % of almond allergic patients. Bet v 1 was able to inhibit IgE‐binding to rPru du 1 by 100%, while rPru du 1 inhibited IgE binding to rBet v 1 by 48%. Pru du 1.0101 activated basophils, though 100‐ to 1000‐fold higher concentrations were required for maximum activation in comparison to rBet v 1.
Conclusion
Considering the strong inhibition capacity and higher allergenic potency of Bet v 1, the results provide compelling evidence for primary sensitization to Bet v 1 in case of birch pollen associated almond allergy. Combining Pru du 6 and Pru du 1 in diagnostic approaches may help to discriminate between primary and birch‐pollen associated almond allergy.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of ...vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (
p
< 0.001) and 41.9% of thrombomodulin (
p
< 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (
p
< 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (
β
= − 0.3 95% confidence interval (CI) − 0.5 to − 0.1), serum level of IL-6 (
β
= − 0.36 95% CI − 0.62 to − 0.1), and thrombomodulin (
β
= − 0.34 95% CI − 0.6 to − 0.08). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.
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