bronchial biopsies
Recently Published Documents


TOTAL DOCUMENTS

174
(FIVE YEARS 41)

H-INDEX

39
(FIVE YEARS 3)

2022 ◽  
pp. 2101634
Author(s):  
Jeanne-Marie Perotin ◽  
Gabrielle Wheway ◽  
Kamran Tariq ◽  
Adnan Azim ◽  
Robert A Ridley ◽  
...  

BackgroundSevere asthma is associated with multiple co-morbidities, including gastro-oesophageal reflux disease (GORD) which can contribute to exacerbation frequency and poor quality of life. Since epithelial dysfunction is an important feature in asthma, we hypothesised that in severe asthma the bronchial epithelium is more susceptible to the effects of acid reflux.MethodsWe developed an in vitro model of GORD using differentiated bronchial epithelial cells (BECs) from normal or severe asthmatic donors exposed to a combination of pepsin, acid pH, and bile acids using a multiple challenge protocol (MCP-PAB). We also analysed bronchial biopsies and undertook RNA-sequencing of bronchial brushings from controls and severe asthmatics without or with GORD.ResultsExposure of BECs to the MCP-PAB caused structural disruption, increased permeability, IL-33 expression, inflammatory mediator release and changes in gene expression for multiple biological processes. Cultures from severe asthmatics were significantly more affected than those from healthy donors. Analysis of bronchial biopsies confirmed increased IL-33 expression in severe asthmatics with GORD. RNA-sequencing of bronchial brushings from this group identified 15 of the top 37 dysregulated genes found in MCP-PAB treated BECs, including genes involved in oxidative stress responses.ConclusionsBy affecting epithelial permeability, GORD may increase exposure of the airway submucosa to allergens and pathogens, resulting in increased risk of inflammation and exacerbations. Clinical implication: These results suggest the need for research into alternative therapeutic management of GORD in severe asthma.


2022 ◽  
pp. 2004361
Author(s):  
Jopeth Ramis ◽  
Robert Middlewick ◽  
Francesco Pappalardo ◽  
Jennifer T. Cairns ◽  
Iain D. Stewart ◽  
...  

Airway smooth muscle cells (ASM) are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyper-responsiveness, and airway remodelling. Extracellular matrix (ECM) can influence tissue remodelling pathways, however, to date no study has investigated the effect of ASM ECM stiffness and crosslinking on the development of asthmatic airway remodelling. We hypothesised that TGFβ activation by ASM is influenced by ECM in asthma and sought to investigate the mechanisms involved. This study combines in vitro and in vivo approaches: human ASM cells were used in vitro to investigate basal TGFβ activation and expression of ECM crosslinking enzymes. Human bronchial biopsies from asthmatic and non-asthmatic donors were used to confirm LOXL2 expression ASM. A chronic ovalbumin model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling. We found that ASM cells from asthmatics activated more TGFβ basally than non-asthmatic controls and that diseased cell-derived ECM influences levels of TGFβ activated. Our data demonstrate that the ECM crosslinking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGFβ activation in vitro, and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an ovalbumin mouse model of asthma. These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217429
Author(s):  
Hugo Farne ◽  
Nicholas Glanville ◽  
Nicholas Johnson ◽  
Tata Kebadze ◽  
Julia Aniscenko ◽  
...  

Background and aimsThe chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.MethodsAtopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.ResultsSix subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0–14 (difference 3.0 (95% CI −29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals.ConclusionTimapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.


Author(s):  
Jenny Calvén ◽  
Christopher Mccrae ◽  
Carina Malmhäll ◽  
Kristina Johansson ◽  
Henric Olsson ◽  
...  

2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.


2021 ◽  
pp. 2101294
Author(s):  
Mirjam P. Roffel ◽  
Ilse M. Boudewijn ◽  
Jos L.L. van Nijnatten ◽  
Alen Faiz ◽  
Corneel J. Vermeulen ◽  
...  

Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls and explored their association with clinical and inflammatory parameters of asthma.Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA-mRNA interactions were analysed using mRNA data available from the same bronchial biopsies and enrichment of pathways was identified with Enrichr and g:Profiler.In total 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared to controls, of which 60 remained differentially expressed after controlling for smoke and inhaled corticosteroid treatment. We identified several asthma associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly and organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies. Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p, as potential regulators that could contribute to the pathogenesis of asthma.


Author(s):  
Anis Mzabi ◽  
Wafa Benzarti ◽  
Wiem Romdhane ◽  
Wafa Baya ◽  
Sana Aissa ◽  
...  

Erythema nodosum (EN) is an inflammatory condition of the subcutaneous fat and has been reported in patients with haematological malignancies (lymphomas) or solid tumours. Lung cancer is the most common cause of paraneoplastic syndrome. We report a case of EN occurring as a paraneoplastic disease. A 48-year-old Tunisian woman, a non-smoker with no relevant medical history, presented with painful, erythematous, firm nodules on her legs with ankle swelling. The patient did not report any other symptoms. There were no abnormalities on examination except for moderate fever. An extensive infectious and immunological investigation was negative. Antistreptolysin antibodies were undetectable. Chest radiography showed a focal opacity in the right lung and a CT scan revealed a mass in the lower right pulmonary lobe with hilar and mediastinal lymphadenopathies, a nodule in the right adrenal gland, condensation in the iliac bone and multiple bilateral nodular cerebral expansive processes. Bronchial biopsies revealed a primitive and moderately differentiated adenocarcinoma. No argument for tuberculosis or sarcoidosis was found.


2021 ◽  
Vol 2 ◽  
Author(s):  
Nil Turan ◽  
T. Anienke van der Veen ◽  
Christina Draijer ◽  
Fatemeh Fattahi ◽  
Nick H. ten Hacken ◽  
...  

Asthma is a heterogenous disease with different inflammatory subgroups that differ in disease severity. This disease variation is hampering treatment and development of new treatment strategies. Macrophages may contribute to asthma phenotypes by their ability to activate in different ways, i.e., T helper cell 1 (Th1)-associated, Th2-associated, or anti-inflammatory activation. It is currently unknown if these different types of activation correspond with specific inflammatory subgroups of asthma. We hypothesized that eosinophilic asthma would be characterized by having Th2-associated macrophages, whereas neutrophilic asthma would have Th1-associated macrophages and both having few anti-inflammatory macrophages. We quantified macrophage subsets in bronchial biopsies of asthma patients using interferon regulatory factor 5 (IRF5)/CD68 for Th1-associated macrophages, CD206/CD68 for Th2-associated macrophages and interleukin 10 (IL10)/CD68 for anti-inflammatory macrophages. Macrophage subset percentages were investigated in subgroups of asthma as defined by unsupervised clustering using neutrophil/eosinophil counts in sputum and tissue and forced expiratory volume in 1 s (FEV1). Asthma patients clustered into four subgroups: mixed-eosinophilic/neutrophilic, paucigranulocytic, neutrophilic with normal FEV1, and neutrophilic with low FEV1, the latter group consisting mainly of smokers. No differences were found for CD206+ macrophages within asthma subgroups. In contrast, IRF5+ macrophages were significantly higher and IL10+ macrophages lower in neutrophilic asthmatics with low FEV1 as compared to those with neutrophilic asthma and normal FEV1 or mixed-eosinophilic asthma. This study shows that neutrophilic asthma with low FEV1 is associated with high numbers of IRF5+, and low numbers of IL10+ macrophages, which may be the result of combined effects of smoking and having asthma.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alastair Watson ◽  
◽  
Lisa Öberg ◽  
Bastian Angermann ◽  
C. Mirella Spalluto ◽  
...  

Abstract Background Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection. Methods We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects. Results ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of –0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES. Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively). Conclusion This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.


2021 ◽  
Author(s):  
Ellen M. B. P. Reuling ◽  
Dwayne D. Naves ◽  
Johannes M. A. Daniels ◽  
Chris Dickhoff ◽  
Pim C. Kortman ◽  
...  

Objective: Recently, 60% discordancy was reported for distinction between typical carcinoid and atypical carcinoid in preoperative biopsy compared to the resection specimen. This study investigated the impact of biopsy surface size, obtained with flexible and rigid bronchoscopy, on diagnostic accuracy of typical and atypical carcinoid. Methods: Biopsy-resection paired specimens of patients referred for treatment to Amsterdam University Medical Centers were retrieved. Bronchial biopsies were obtained either by flexible or rigid biopsy. The definitive diagnosis was based on the resection specimen. Diagnosis according to the 2015 WHO classification, mitoses and necrosis in biopsy and resection specimen, were independently re-evaluated by two pathologists. Results: After screening 298 patients, 64 biopsy-resection pairs with available tissue were included of which 34 (53%) were biopsied with flexible and 30 (47%) with rigid biopsy. In 35 (55%) patients, the tumor classification between the biopsy and resection specimen was concordant. The discordance in the remaining 29 cases (45%) was caused by misclassification of atypical as typical carcinoid in bronchoscopy specimens, predominantly in small flexible biopsies (59%, p=0.021). Of biopsies measuring <2 mm2, 79% were classified as discordant and 52% of the discordant biopsies measured <4 mm2. Conclusion: Histological classification in central carcinoid tumors is discordant in 45% of the biopsies, with increasing diagnostic accuracy in larger biopsies. Distinguishing carcinoid tumor into typical or atypical carcinoid on biopsies <4 mm2 should be discouraged. A cumulative biopsy surface of at least 4 mm2 tumor is preferred to increase the diagnostic accuracy which helps in optimal treatment planning.


Sign in / Sign up

Export Citation Format

Share Document