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F1000Research 2020Bronchiolitis is injury to the bronchioles (small airways with a diameter of 2 mm or less) resulting in inflammation and/or fibrosis. Bronchioles can be involved in... (Review)
Review
Bronchiolitis is injury to the bronchioles (small airways with a diameter of 2 mm or less) resulting in inflammation and/or fibrosis. Bronchioles can be involved in pathologic processes that involve predominantly the lung parenchyma or large airways, but, in some diseases, bronchioles are the main site of injury ("primary bronchiolitis"). Acute bronchiolitis caused by viruses is responsible for most cases of bronchiolitis in infants and children. In adults, however, there is a wide spectrum of bronchiolar disorders and most are chronic. Many forms of bronchiolitis have been described in the literature, and the terminology in this regard remains confusing. In clinical practice, a classification scheme based on the underlying histopathologic pattern (correlates with presenting radiologic abnormalities) facilitates the recognition of bronchiolitis and the search for the inciting cause of the lung injury. Respiratory bronchiolitis is the most common form of bronchiolitis in adults and is usually related to cigarette smoking. Currently, the diagnosis of respiratory bronchiolitis is generally achieved based on the clinical context (smoking history) and chest CT findings. Constrictive (obliterative) bronchiolitis is associated with airflow obstruction and is seen in various clinical contexts including environmental/occupational inhalation exposures, transplant recipients (bronchiolitis obliterans syndrome), and many others. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is increasingly recognized and can be associated with progressive airflow obstruction related to constrictive bronchiolitis ("DIPNECH syndrome"). Diffuse aspiration bronchiolitis is a form of aspiration-related lung disease that is often unsuspected and confused for interstitial lung disease. Novel forms of bronchiolitis have been described, including lymphocytic bronchiolitis and alveolar ductitis with emphysema recently described in employees at a manufacturing facility for industrial machines. Bronchiolitis is also a component of vaping-related lung injury encountered in the recent outbreak.
Topics: Adult; Bronchiolitis; Humans; Inflammation; Tomography, X-Ray Computed; Vaping
PubMed: 32551095
DOI: 10.12688/f1000research.21778.1 -
Frontiers in Pediatrics 2022Recent studies identified a great diversity of cell types in precise number and position to create the architectural features of the lung that ventilation and...
BACKGROUND
Recent studies identified a great diversity of cell types in precise number and position to create the architectural features of the lung that ventilation and respiration at birth depend on. With damaged respiratory function at birth, congenital diaphragmatic hernia (CDH) is one of the more severe causes of fetal lung hypoplasia with unspecified cellular dynamics.
OBJECTIVES
To characterize the epithelial cell tissue in hypoplastic lungs, a careful analysis regarding pulmonary morphology and epithelial cell profile was conducted from pseudoglandular-to-saccular phases in normal versus nitrofen-induced CDH rat lungs.
DESIGN
Our analysis comprises three experimental groups, control, nitrofen (NF) and CDH, in which the relative expression levels (western blot) by group and developmental stage were analyzed in whole lung. Spatiotemporal distribution (immunohistochemistry) was revealed by pulmonary structure during normal and hypoplastic fetal lung development. Surfactant protein-C (SP-C), calcitonin gene-related peptide (CGRP), clara cell secretory protein (CCSP), and forkhead box J1 (FOXJ1) were the used molecular markers for alveolar epithelial cell type 2 (AEC2), pulmonary neuroendocrine, clara, and ciliated cell profiles, respectively.
RESULTS
Generally, we identified an aberrant expression of SP-C, CGRP, CCSP, and FOXJ1 in nitrofen-exposed lungs. For instance, the overexpression of FOXJ1 and CGRP in primordia of bronchiole defined the pseudoglandular stage in CDH lungs, whereas the increased expression of CGRP in bronchi; FOXJ1 and CGRP in terminal bronchiole; and SP-C in BADJ classified the canalicular and saccular stages in hypoplastic lungs. We also described higher expression levels in NF than CDH or control groups for both FOXJ1 in bronchi, terminal bronchiole and BADJ at canalicular stage, and SP-C in bronchi and terminal bronchiole at canalicular and saccular stages. Finally, we report an unexpected expression of FOXJ1 in BADJ at canalicular and saccular stages, whereas the multi cilia observed in bronchi were notably absent at embryonic day 21.5 in induced-CDH lungs.
CONCLUSION
The recognized alterations in the epithelial cell profile contribute to a better understanding of neonatal respiratory insufficiency in induced-CDH lungs and indicate a problem in the epithelial cell differentiation in hypoplastic lungs.
PubMed: 35601428
DOI: 10.3389/fped.2022.836591 -
Expert Review of Respiratory Medicine Nov 2018Acute exacerbations of chronic lung disease account for substantial morbidity and health costs. Repeated inflammatory episodes and attendant bronchoconstriction cause... (Review)
Review
Acute exacerbations of chronic lung disease account for substantial morbidity and health costs. Repeated inflammatory episodes and attendant bronchoconstriction cause structural remodeling of the airway. Remodeling is a multicellular response to mucosal injury that results in epithelial cell-state changes, enhanced extracellular deposition, and expansion of pro-fibrotic myofibroblast populations. Areas covered: This manuscript overviews mechanistic studies identifying key sentinel cell populations in the airway and how pattern recognition signaling induces maladaptive mucosal changes and airway remodeling. Studies elucidating how NFκB couples with an atypical histone acetyltransferase, bromodomain-containing protein 4 (BRD4) that reprograms mucosal fibrogenic responses, are described. The approaches to development and characterization of selective inhibitors of epigenetic reprogramming on innate inflammation and structural remodeling in preclinical models are detailed. Expert commentary: Bronchiolar cells derived from Scgb1a1-expressing progenitors function as major sentinel cells of the airway, responsible for initiating antiviral and aeroallergen responses. In these sentinel cells, activation of innate inflammation is coupled to neutrophilic recruitment, mesenchymal transition and myofibroblast expansion. Therapeutics targeting the NFkB-BRD4 may be efficacious in reducing pathological effects of acute exacerbations in chronic lung disease.
Topics: Adaptive Immunity; Airway Remodeling; Allergens; Asthma; Bronchial Hyperreactivity; Bronchioles; Cell Cycle Proteins; Environmental Exposure; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans; Immunity, Innate; Myofibroblasts; NF-kappa B p50 Subunit; Nuclear Proteins; Pulmonary Disease, Chronic Obstructive; Receptors, Pattern Recognition; Respiratory Mucosa; Toll-Like Receptors; Transcription Factors; Virus Diseases
PubMed: 30241450
DOI: 10.1080/17476348.2018.1526677 -
Frontiers in Immunology 2023COPD is characterized by chronic airway inflammation, small airways changes, with disappearance and obstruction, and also distal/alveolar destruction (emphysema). The...
RATIONALE
COPD is characterized by chronic airway inflammation, small airways changes, with disappearance and obstruction, and also distal/alveolar destruction (emphysema). The chronology by which these three features evolve with altered mucosal immunity remains elusive. This study assessed the mucosal immune defense in human control and end-stage COPD lungs, by detailed microCT and RNA transcriptomic analysis of diversely affected zones.
METHODS
In 11 control (non-used donors) and 11 COPD (end-stage) explant frozen lungs, 4 cylinders/cores were processed per lung for microCT and tissue transcriptomics. MicroCT was used to quantify tissue percentage and alveolar surface density to classify the COPD cores in mild, moderate and severe alveolar destruction groups, as well as to quantify terminal bronchioles in each group. Transcriptomics of each core assessed fold changes in innate and adaptive cells and pathway enrichment score between control and COPD cores. Immunostainings of immune cells were performed for validation.
RESULTS
In mildly affected zones, decreased defensins and increased mucus production were observed, along CD8+ T cell accumulation and activation of the IgA pathway. In more severely affected zones, CD68+ myeloid antigen-presenting cells, CD4+ T cells and B cells, as well as MHCII and IgA pathway genes were upregulated. In contrast, terminal bronchioles were decreased in all COPD cores.
CONCLUSION
Spatial investigation of end-stage COPD lungs show that mucosal defense dysregulation with decreased defensins and increased mucus and IgA responses, start concomitantly with CD8+ T-cell accumulation in mild emphysema zones, where terminal bronchioles are already decreased. In contrast, adaptive Th and B cell activation is observed in areas with more advanced tissue destruction. This study suggests that in COPD innate immune alterations occur early in the tissue destruction process, which affects both the alveoli and the terminal bronchioles, before the onset of an adaptive immune response.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Inflammation; Emphysema; Defensins; Immunoglobulin A
PubMed: 37915582
DOI: 10.3389/fimmu.2023.1275845 -
Cells May 2022Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options, and there is a huge unmet need for new therapies. A growing... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options, and there is a huge unmet need for new therapies. A growing body of evidence suggests that the histone deacetylase (HDAC) family of transcriptional corepressors has emerged as crucial mediators of IPF pathogenesis. HDACs deacetylate histones and result in chromatin condensation and epigenetic repression of gene transcription. HDACs also catalyse the deacetylation of many non-histone proteins, including transcription factors, thus also leading to changes in the transcriptome and cellular signalling. Increased HDAC expression is associated with cell proliferation, cell growth and anti-apoptosis and is, thus, a salient feature of many cancers. In IPF, induction and abnormal upregulation of Class I and Class II HDAC enzymes in myofibroblast foci, as well as aberrant bronchiolar epithelium, is an eminent observation, whereas type-II alveolar epithelial cells (AECII) of IPF lungs indicate a significant depletion of many HDACs. We thus suggest that the significant imbalance of HDAC activity in IPF lungs, with a "cancer-like" increase in fibroblastic and bronchial cells versus a lack in AECII, promotes and perpetuates fibrosis. This review focuses on the mechanisms by which Class I and Class II HDACs mediate fibrogenesis and on the mechanisms by which various HDAC inhibitors reverse the deregulated epigenetic responses in IPF, supporting HDAC inhibition as promising IPF therapy.
Topics: Fibroblasts; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Humans; Idiopathic Pulmonary Fibrosis; Transcription Factors
PubMed: 35626663
DOI: 10.3390/cells11101626 -
An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease.American Journal of Physiology. Lung... May 2023Club cells are found in human small airways where they play an important role in immune defense, xenobiotic metabolism, and repair after injury. Over the past few years,... (Review)
Review
Club cells are found in human small airways where they play an important role in immune defense, xenobiotic metabolism, and repair after injury. Over the past few years, data from single-cell RNA sequencing (scRNA-seq) studies has generated new insights into club cell heterogeneity and function. In this review, we integrate findings from scRNA-seq experiments with earlier in vitro, in vivo, and microscopy studies and highlight the many ways club cells contribute to airway homeostasis. We then discuss evidence for loss of club cells or club cell products in the airways of patients with chronic obstructive pulmonary disease (COPD) and discuss potential mechanisms through which this might occur.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Bronchioles; Epithelial Cells
PubMed: 36942863
DOI: 10.1152/ajplung.00192.2022 -
ERJ Open Research May 2023The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence...
BACKGROUND
The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis stratification of the presence (TW) or absence (TW) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors.
METHODS
In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW and TW groups. We ascertained radiological progression at 5 years CT and EB-OCT.
RESULTS
We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW group than in the TWgroup. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW group. At 5 years, 53.1% of patients in the TW group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW group (p<0.05). 34 patients in the TW group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW bronchioles on CT predicted progression of bronchiectasis.
CONCLUSION
Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.
PubMed: 37377656
DOI: 10.1183/23120541.00490-2022 -
Pharmaceuticals (Basel, Switzerland) Nov 2016Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral... (Review)
Review
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of "chemosensor", detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists.
PubMed: 27827953
DOI: 10.3390/ph9040070 -
Respirology (Carlton, Vic.) Feb 2016Although in many Western countries levels of ambient air pollution have been improving with the setting of upper limits and better urban planning, air pollution in... (Review)
Review
Although in many Western countries levels of ambient air pollution have been improving with the setting of upper limits and better urban planning, air pollution in developing countries and particularly those with rapid industrialization has become a major global problem. Together with increased motor vehicle ownership and traffic congestion, there is a growing issue with airborne particles of respirable size. These particles are thought responsible for respiratory and cardiovascular effects and have also been implicated in cancer pathogenesis. The pathologic effects in the lung are mediated via inflammatory pathways and involve oxidative stress similar to cigarette smoking. These effects are seen in the peripheral airways where the smaller particle fractions are deposited and lead to airway remodelling. However, emphysema and loss of bronchioles seen with cigarette smoking have not been described with ambient air pollution, and there are few studies specifically looking at peripheral airway function. Definitive evidence of air pollution causing COPD is lacking and a different study design is required to link air pollution and COPD.
Topics: Air Pollutants; Air Pollution; Airway Remodeling; Bronchioles; Humans; Oxidative Stress; Particulate Matter; Pulmonary Disease, Chronic Obstructive
PubMed: 26412571
DOI: 10.1111/resp.12644 -
The Journal of Pathology Jan 2015Infants and young children with acute onset of wheezing and reduced respiratory airflows are often diagnosed with obstruction and inflammation of the small bronchiolar... (Review)
Review
Infants and young children with acute onset of wheezing and reduced respiratory airflows are often diagnosed with obstruction and inflammation of the small bronchiolar airways, ie bronchiolitis. The most common aetological agents causing bronchiolitis in young children are the respiratory viruses, and of the commonly encountered respiratory viruses, respiratory syncytial virus (RSV) has a propensity for causing bronchiolitis. Indeed, RSV bronchiolitis remains the major reason why previously healthy infants are admitted to hospital. Why RSV infection is such a predominant cause of bronchiolitis is the subject of this review. By reviewing the available histopathology of RSV bronchiolitis, both in humans and relevant animal models, we identify hallmark features of RSV infection of the distal airways and focus attention on the consequences of columnar cell cytopathology occurring in the bronchioles, which directly impacts the development of bronchiolar obstruction, inflammation and disease.
Topics: Animals; Biopsy; Bronchioles; Bronchiolitis; Disease Models, Animal; Host-Pathogen Interactions; Humans; Pathology, Molecular; Predictive Value of Tests; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Risk Factors; Severity of Illness Index; Virology; Virulence
PubMed: 25302625
DOI: 10.1002/path.4462