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Nature Feb 2020Tobacco smoking causes lung cancer, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA. The profound effects of...
Tobacco smoking causes lung cancer, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA. The profound effects of tobacco on the genome of lung cancer cells are well-documented, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bronchi; Child; Clone Cells; DNA Mutational Analysis; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutagenesis; Mutation; Respiratory Mucosa; Smokers; Telomere; Tobacco Smoking; Young Adult
PubMed: 31996850
DOI: 10.1038/s41586-020-1961-1 -
Allergy Aug 2020We found that HBEC expressed the IL-5 receptor, which triggered intracellular signaling and changed gene expression. This data indicate that in addition to targeting...
We found that HBEC expressed the IL-5 receptor, which triggered intracellular signaling and changed gene expression. This data indicate that in addition to targeting eosinophils, IL-5 and anti-IL-5 biologics may have a direct role on AEC.
Topics: Bronchi; Cells, Cultured; Epithelial Cells; Humans; Interleukin-13; Receptors, Interleukin-5
PubMed: 32246831
DOI: 10.1111/all.14297 -
Life Sciences Mar 2021Pyroptosis and inflammation are involved in the development of chronic obstructive pulmonary disease (COPD). However, the cigarette smoke-mediated mechanism of COPD...
AIMS
Pyroptosis and inflammation are involved in the development of chronic obstructive pulmonary disease (COPD). However, the cigarette smoke-mediated mechanism of COPD remains unclear. In this study, we aimed to investigate the role of nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome-mediated pyroptosis in the death of human bronchial epithelial (HBE) cells after cigarette smoke extract (CSE) exposure.
MAIN METHODS
The protein level of NLRP3 in lung tissue was measured after cigarette smoke exposure in vivo. In vitro, HBE cells were treated with CSE. Subsequently, the activity of caspase-1, lactate dehydrogenase (LDH) release, release of interleukin (IL)-1β and NLRP3 expression levels were measured. The involvement of reactive oxygen species (ROS) was also explored.
KEY FINDINGS
After exposure to CSE, increased release of LDH, the transcriptional and translational upregulation of NLRP3, the caspase-1 activity levels, and enhanced IL-1β and IL-18 release were observed in 16HBE cells. In addition, NLRP3 was required to activate the caspase-1. Our results suggested that pre-stimulated of 16HBE with a caspase-1 inhibitor, or using NLRP3 siRNA to silence NLRP3 expression, also caused the decrease of IL-1β release and pyroptosis.
SIGNIFICANCES
CSE induced inflammation and contributed to pyroptosis through the ROS/NLRP3/caspase-1 pathway in 16HBE cells. The NLRP3 inflammasome participates in CSE-induced HBE cell damage and pyroptosis, which could provide new insights into COPD.
Topics: Animals; Bronchi; Caspase 1; Disease Models, Animal; Epithelial Cells; Humans; Inflammasomes; Inflammation; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pyroptosis; Reactive Oxygen Species; Signal Transduction; Smoke; Nicotiana
PubMed: 33465393
DOI: 10.1016/j.lfs.2021.119090 -
Jornal Brasileiro de Pneumologia :... Mar 2020
Topics: Bronchi; Bronchoscopy; Humans; Lung; Pulmonary Aspergillosis
PubMed: 32130335
DOI: 10.36416/1806-3756/e20190279 -
Panminerva Medica Sep 2019Over the last decade transbronchial lung cryobiopsy (TBLC) has proven to be an "innovative application" of an "old procedure" for the histologic diagnosis of diffuse... (Review)
Review
Over the last decade transbronchial lung cryobiopsy (TBLC) has proven to be an "innovative application" of an "old procedure" for the histologic diagnosis of diffuse interstitial lung diseases (DILDs). Thus, the technique of TBL cryobiopsy is now adopted for diagnostic purposes, transbronchially in peripheral airways to sample lung parenchyma, whereas this same technique was traditionally employed in the past for therapeutic purposes, essentially for the management of malignant obstruction of central airways. When patients with interstitial lung diseases (ILDs) need histopathological data in their diagnostic pathway, this bioptic approach could be a valid alternative to surgical lung biopsy, that is still the gold standard at the moment. TBL cryobiopsy has a good safety profile, its sensitivity and specificity appear good overall in idiopathic pulmonary fibrosis. In the last ten years, many papers have been published about this procedure defining modalities by which cryobiopsy should be performed. These studies have shown that TBL cryobiopsy is feasible, it allows to obtain larger lung parenchymal specimens (3 times larger than "classic" transbronchial biopsies), characterized by unaltered and artefact-free morphology, and it represents a safe and poorly invasive diagnostic tool for the histologic diagnosis of ILDs. The technical aspects are really important, and they still need a complete standardization. TBL cryobiopsy should be part of an equipment of the modern interventional pulmonologist, who should know indications and contraindications of this methodic and the technical aspects of the procedure. This is a complex procedure requiring to be performed by endoscopists working in specialized centers with specific knowledge of DILDs, and a multidisciplinary approach, which represent pre-requisites for admission to training in this procedure.
Topics: Biopsy; Bronchi; Bronchoscopy; Clinical Competence; Cold Temperature; Cryosurgery; Endoscopy; Humans; Lung; Lung Diseases, Interstitial; Pulmonary Medicine; Sensitivity and Specificity
PubMed: 30394714
DOI: 10.23736/S0031-0808.18.03567-X -
Pneumologie (Stuttgart, Germany) Jul 2020Cryosurgery has been successfully in bronchoscopy for several years. In addition to the local therapy of tumors and stenoses, cryo extraction enables the endobronchial...
Cryosurgery has been successfully in bronchoscopy for several years. In addition to the local therapy of tumors and stenoses, cryo extraction enables the endobronchial and transbronchial extraction of large, high-quality biopsies. This is with regard to the diagnosis of diffuse lung diseases and the molecular analysis of malignant lung tumors of outstanding importance. This article explains the method and implementation of transbronchial cryobiopsy.
Topics: Biopsy; Bronchi; Bronchoscopy; Cryosurgery; Humans; Lung; Lung Diseases; Pulmonary Medicine
PubMed: 32674192
DOI: 10.1055/a-0761-2551 -
European Respiratory Review : An... Mar 2022Tracheobronchial injury is a heterogeneous entity comprising multiple rare and potentially life-threatening scenarios. We performed a systematic literature review... (Review)
Review
Tracheobronchial injury is a heterogeneous entity comprising multiple rare and potentially life-threatening scenarios. We performed a systematic literature review focusing on post-intubation tracheal injuries (PiTIs) and post-traumatic tracheobronchial injuries (PTTBIs).PiTIs are often longitudinal lacerations of the middle third of the membranous trachea. Subcutaneous emphysema of the face and trunk following tracheal intubation should immediately trigger the diagnosis. Diagnosis may be suspected on the chest computed tomography (CT) and should be confirmed by bronchoscopic examination. Conservative management is encouraged for a spontaneously breathing or stable patient on noninvasive ventilation. Surgical repair is mandatory when mechanical ventilation is required and if bridging of the injury is impossible.PTTBIs are often associated with other severe injuries. Patients often present with massive subcutaneous emphysema and intractable pneumothorax. Diagnosis may be suspected on the chest CT and should be confirmed by bronchoscopic examination. Early surgical repair is indicated. In selected patients, conservative management can be considered.
Topics: Bronchi; Humans; Intubation, Intratracheal; Noninvasive Ventilation; Tomography, X-Ray Computed; Trachea
PubMed: 35082126
DOI: 10.1183/16000617.0126-2021 -
Current Topics in Microbiology and... 2020Pulmonary respiration inevitably exposes the mucosal surface of the lung to potentially noxious stimuli, including pathogens, allergens, and particulates, each of which... (Review)
Review
Pulmonary respiration inevitably exposes the mucosal surface of the lung to potentially noxious stimuli, including pathogens, allergens, and particulates, each of which can trigger pulmonary damage and inflammation. As inflammation resolves, B and T lymphocytes often aggregate around large bronchi to form inducible Bronchus-Associated Lymphoid Tissue (iBALT). iBALT formation can be initiated by a diverse array of molecular pathways that converge on the activation and differentiation of chemokine-expressing stromal cells that serve as the scaffolding for iBALT and facilitate the recruitment, retention, and organization of leukocytes. Like conventional lymphoid organs, iBALT recruits naïve lymphocytes from the blood, exposes them to local antigens, in this case from the airways, and supports their activation and differentiation into effector cells. The activity of iBALT is demonstrably beneficial for the clearance of respiratory pathogens; however, it is less clear whether it dampens or exacerbates inflammatory responses to non-infectious agents. Here, we review the evidence regarding the role of iBALT in pulmonary immunity and propose that the final outcome depends on the context of the disease.
Topics: Bronchi; Humans; Immunity, Mucosal; Lymphocytes; Respiration
PubMed: 31974759
DOI: 10.1007/82_2019_191 -
Respirology (Carlton, Vic.) Sep 2022Since the publication of a sham-controlled, randomized trial (AIR2) and subsequent marketing approval by the US Food and Drug Administration, we have significantly... (Review)
Review
Since the publication of a sham-controlled, randomized trial (AIR2) and subsequent marketing approval by the US Food and Drug Administration, we have significantly advanced our understanding of bronchial thermoplasty (BT)'s scientific basis, long-term safety, clinical efficacy and cost-effectiveness. In particular, the last 2 years have witnessed multiple research publications on several of these counts. In this review, we critically appraise our evolving understanding of BT's biologic underpinnings and clinical impact, offer an evidence-based patient workflow guide for the busy pulmonologist and highlight both current challenges as well as potential solutions for the researcher and the clinician.
Topics: Asthma; Bronchi; Bronchial Thermoplasty; Cost-Benefit Analysis; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35692074
DOI: 10.1111/resp.14312 -
Internal Medicine (Tokyo, Japan) Apr 2020A 77-year-old man with anemia who had undergone 2 abdominal surgeries for colon and gastric cancer experienced dyspnea after swallowing a patency capsule before...
A 77-year-old man with anemia who had undergone 2 abdominal surgeries for colon and gastric cancer experienced dyspnea after swallowing a patency capsule before endoscopy for investigating the cause of anemia. Chest radiography and computed tomography revealed that the patency capsule was located within the bronchus intermedius. It was successfully removed by flexible bronchoscopy. The balloon was placed over the capsule and inflated. Subsequently, the catheter was pulled, while thus dragging the capsule with it and preventing its destruction. In cases of patency capsule aspiration, the capsule must be removed without deformity, before it causes inflammation by releasing barium into the airway.
Topics: Aged; Bronchi; Bronchoscopy; Capsule Endoscopy; Foreign Bodies; Humans; Male; Respiratory Aspiration; Tomography, X-Ray Computed
PubMed: 31915319
DOI: 10.2169/internalmedicine.4012-19