Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway ...epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (
= 21) vs. no persistent (
= 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g.,
,
,
, and
) and inhibiting apoptosis (e.g., higher mRNA expression of
,
,
, and lower of
,
,
). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (
,
), involved in ECM remodeling (
), neovascularization (
,
), nerve functioning (
,
), oxidative stress adaptation (
,
), epigenetic modifications (
,
), and the innate immune response (
,
). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.
Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic ...feature frequent in severe asthma, bronchial epithelial transcriptome, and functional and structural measures of airway remodeling. We compared epithelial gene expression, spirometry, airway cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), and blood and bronchoalveolar lavage (BAL) cytokines of
= 40 moderate to severe eosinophilic (EA) and non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA patients showed a similar extent of airway remodeling as NEA but had an increased expression of genes involved in the immune response and inflammation (e.g.,
), reactive oxygen species generation (
,
), cell activation and proliferation (
), cargo transporting (
,
), and tissue remodeling (
,
,
), and a lower expression of genes involved in epithelial integrity (e.g.,
) and histone acetylation (
). Genes co-expressed in EA were involved in antiviral responses (e.g.,
), cell migration (
,
), cell adhesion (
), epithelial-mesenchymal transition (
), and airway hyperreactivity and remodeling (
,
), and several were linked to asthma in genome- (e.g.,
,
) or epigenome-wide association studies (
,
,
,
). Signaling pathways inferred from the co-expression pattern were associated with airway remodeling (e.g., TGF-β/Smad2/3, E2F/Rb, and Wnt/β-catenin).
Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of ...β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.
Airway inflammation in asthma is related to increased reactive oxygen species generation, potentially leading to tissue injury and subsequent airway remodeling. We evaluated oxidative stress in ...peripheral blood from asthmatic subjects (n = 74) and matched controls (n = 65), using recently developed real-time monitoring of the protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also investigated the relation of the systemic oxidative stress response in asthma to disease severity, lung function, airway remodeling indices (lung computed tomography and histology), and blood and bronchoalveolar lavage fluid (BAL) inflammatory biomarkers. We documented enhanced systemic oxidative stress in asthma, reflected by 35% faster and 58% higher cumulative fluorescent product generation in the CBA assay (p < 0.001 for both). The dynamics of HP generation correlated inversely with lung function but not with asthma severity or histological measures of airway remodeling. HP generation was associated positively with inflammatory indices in the blood (e.g., C-reactive protein) and BAL (e.g., interleukin IL-6, IL-12p70, and neutrophil count). Bronchial obstruction, thicker airway walls, increased BAL IL-6, and citrullinated histone 3 in systemic circulation independently determined increased HP formation. In conclusion, a real-time CBA assay showed increased systemic HP generation in asthma. In addition, it was associated with inflammatory biomarkers, suggesting that proper disease control can also lead to a decrease in oxidative stress.
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.
The goal of this paper is to describe the approach for automatic identifying human organs from a medical CT images and discuss results of its comparison to different classification methods. The main ...premise of this approach is the use of data sets together with the relevant domain knowledge. We test our approach on multiple CT images of chest organs (trachea, lungs, bronchus) and demonstrate usefulness and effectiveness of the resulting classifications. The presented approach can be used to assist in solving more complex medical problems.
Aspirin-induced asthma/rhinitis (AIAR) is characterized by the altered metabolism of leukotrienes and proinflammatory prostaglandins. The basal and postchallenge levels of eicosanoids might reflect ...the clinical and biochemical characteristics of patients with distinct types of hypersensitive responses to aspirin.
We compared clinical and eicosanoid profiles of patients with AIAR showing both bronchial and nasal versus isolated nasal responses to aspirin challenge.
Twenty-three patients with AIAR underwent the single-blind, oral, placebo-controlled aspirin challenge. The bronchial response (BR) was evidenced by dyspnea and spirometry, whereas the nasal response (NR) was evidenced by nasal symptoms and acoustic rhinometry and/or rhinomanometry. Urinary leukotriene E
4 (uLTE
4), serum and urinary stable prostaglandin D
2 metabolite, and 9α,11β-prostaglandin F
2 (9α,11β-PGF
2), were determined at baseline and after the aspirin challenge.
Fifteen subjects showed BR and NR (BNR), whereas 8 showed NR only. Basal uLTE
4 in the BNR group was significantly higher than in the NR group. After aspirin challenge, it increased significantly in both groups. Serum 9α,11β-PGF
2increased after aspirin challenge in the BNR group only. The patients with BNR had more severe AIAR.
BNR to aspirin in AIAR indicates a more advanced disease and more profound underlying eicosanoid metabolism disturbances.
Based on the analysis and interpretation of maps, remote sensing data published in the literature, and environmental reconnaissance, this article discusses environmental transformations in the ...Wojkowice area in southern Poland (up to the year 2020). A comprehensive analysis was carried out concerning spatial development, mining activity, hydrogeological conditions and the biotic environment. The current state of the hydrogeological conditions was also characterized. Mining activity in the vicinity of the studied town caused significant changes in its relief, which contributed to its area dropping by about 5 m. In fact, these terrain forms are overgrown by various forms of vegetation that colonized these areas both naturally and as a result of forest reclamation. The contemporary vegetation of Wojkowice differs from the potential natural vegetation, which is an indicator of the complete anthropogenization of the natural environment. Over 100 years of industrial activity in Wojkowice has also contributed to a strong transformation of the groundwater. There has been a quantitative depletion of usable groundwater in the Triassic and Carboniferous formations. With inflows to the ore mines of up to 17 m3/min, the groundwater table has dropped by more than 60 m. The aquifer of Muschelkalk has been practically drained. At present, wells extract the waters from the Röth aquifer. There has been a major transformation of groundwater chemistry. The waters of the Triassic carbonate complex are anthropogenically transformated and are characterized by increased mineralization, multi-ionic types and usually with a quality class III and IV, and, therefore, they require some treatment.
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