In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function

<p>Abstract</p> <p>Background</p> <p>Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by <it>in vitro </it>spectral analysis of elastin powder. We hypothesized that FCFM images capture <it>in vivo </it>elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated.</p> <p>Methods</p> <p>In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls) spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κ_w.</p> <p>Results</p> <p>The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κ_w0.744). The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV₁%predicted between the different patterns by histology (p = 0.001) and FCFM (p = 0.048), regardless of asthma or atopy.</p> <p>Conclusion</p> <p>FCFM captures the elastic fibre pattern within the airway wall in humans <it>in vivo</it>. The association between post-bronchodilator FEV₁%predicted and both histological and FCFM elastic fibre patterns points towards a structure-function relationship between extracellular matrix in the airway wall and lung function.</p> <p>Trial registration</p> <p>Netherlands Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=NTR1306">NTR1306</a></p

Frecuencia de parásitos sanguíneos en la zona de influencia de la Facultad de Ciencias Veterinarias de la Universidad Nacional del Litoral, período 2017-2018 : preliminares

Los hemoparásitos son organismos responsables de enfermedades de gran trascendencia para la salud animal y salud pública a nivel mundial En la zona de influencia de la Facultad de Ciencias Veterinarias de la UNL (Santa Fe) no hay datos certeros de prevalencia, reportándose sólo hallazgos accidentales. El objetivo del presente estudio es describir la frecuencia de hemoparásitos hallados a partir de frotis sanguíneos durante el período comprendido desde agosto de 2017 al mayo de 2018. De cada muestra de sangre se realizaron dos extendidos sanguíneos para la búsqueda de hemoparásitos mediante la observación microscópica. Se procesaron 200 muestras, de las cuales 32 (16%) resultaron positivas. Se encontró Anaplasma platys, Hepatozoon canis, Dirofilaria immitis, Ehrlichia canis y piroplasmas. El presente trabajo aporta datos relevantes para la zona de influencia de la Facultad de Ciencias Veterinarias debido a que los hallazgos constituyen el primer reporte de la provincia de Santa FeFil: Von der Thüsen, Santiago. Universidad Nacional del LitoralFil: Pontarelli, Fiorela. Universidad Nacional del LitoralFil: Valler, Ebelyn. Universidad Nacional del Litora

Artificial intelligence-based recurrence prediction outperforms classical histopathological methods in pulmonary adenocarcinoma biopsies

Introduction: Between 10 and 50% of early-stage lung adenocarcinoma patients experience local or distant recurrence. Histological parameters such as a solid or micropapillary growth pattern are well-described risk factors for recurrence. However, not every patient presenting with such a pattern will develop recurrence. Designing a model which can more accurately predict recurrence on small biopsy samples can aid the stratification of patients for surgery, (neo-)adjuvant therapy, and follow-up. Material and Methods: In this study, a statistical model on biopsies fed with histological data from early and advanced-stage lung adenocarcinomas was developed to predict recurrence after surgical resection. Additionally, a convolutional neural network (CNN)-based artificial intelligence (AI) classification model, named AI-based Lung Adenocarcinoma Recurrence Predictor (AILARP), was trained to predict recurrence, with an ImageNet pre-trained EfficientNet that was fine-tuned on lung adenocarcinoma biopsies using transfer learning. Both models were validated using the same biopsy dataset to ensure that an accurate comparison was demonstrated. Results: The statistical model had an accuracy of 0.49 for all patients when using histology data only. The AI classification model yielded a test accuracy of 0.70 and 0.82 and an area under the curve (AUC) of 0.74 and 0.87 on patch-wise and patient-wise hematoxylin and eosin (H&amp;E) stained whole slide images (WSIs), respectively. Conclusion: AI classification outperformed the traditional clinical approach for recurrence prediction on biopsies by a fair margin. The AI classifier may stratify patients according to their recurrence risk, based only on small biopsies. This model warrants validation in a larger lung biopsy cohort.</p

Engineering of pulmonary surfactant corona on inhaled nanoparticles to operate in the lung system

Exposure of inhaled nanoparticles (NPs) to the deep lung tissue results in the adsorption of pulmonary surfactant (PSf) on the surface of NPs and the formation of a biomolecular corona. The adsorption of the peculiar phospholipids (PLs) and surfactant proteins (SPs) provides NPs with a new bio-identity, which likely changes their corresponding interactions with cells and other bio-systems. Exploring the interaction of NPs with the PSf film at the alveolar air-fluid interface can provide valuable insights into the role of biofluids in the cellular uptake of NPs and their nanotoxic effects. Wrapping biomembranes around NPs and the formation of lipoprotein corona regulate viscoelastic changes, NP insertion into the membrane, and cellular uptake of NPs. In this review, a concise overview has been presented on the engineering of PSf on inhaled NPs to operate in lung environment. First, the physiological barriers in the pulmonary delivery of NPs and approaches to regulating their pulmonary fate are introduced and rationalized. Next, a short description is given on the different sources used for exploring the interfacial performance of inhaled NPs in vitro. A discussion is then presented on SP corona formation on the surface of inhaled NPs, coronal proteome/lipidome in respiratory tract lining fluid (RTLF), regulation of NP aggregation and surfactant flow characteristics, PSf corona and its functional role in the cellular uptake of NPs, followed by explanations on the clinical correlations of PSf corona formation/inhibition on the surface of NPs. Finally, the challenges and future perspectives of the field have been discussed. This review can be harnessed to exploit PSf for the development of safe and bio-inspired pulmonary drug delivery strategies.</p

Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software-assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS− M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.</p