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International Journal of Chronic... 2022Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis, emphysema, and small airway obstruction. Incompletely reversible airflow limitation,... (Review)
Review
Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis, emphysema, and small airway obstruction. Incompletely reversible airflow limitation, inflammation, excessive mucus secretion and bronchial mucosal epithelial lesions are the main pathological basis of the disease. The prevalence of COPD is increasingly worldwide, which has caused the burden on individuals and society. This paper summarizes the pathogenesis of COPD and clarifies the effect and mechanism of the latest targeted drugs for COPD. Besides, we focus on NOD-like receptor thermal protein domain associated protein 3 inflammasome (NLRP3 inflammasome). NLRP3 can promote production of interleukin-1β (IL-1β) and interleukin-18 (IL-18). NLRP3 is an important factor in the migratory aggregation of macrophages and neutrophils and the generation of oxidative stress. Inhibition of NLRP3 inflammasome indirectly blocks the inflammatory effects of IL-1β and IL-18, which may be regarded as an ideal target for COPD treatment.
Topics: Humans; Inflammasomes; Inflammation; Interleukin-18; Interleukin-1beta; NLR Family, Pyrin Domain-Containing 3 Protein; Pulmonary Disease, Chronic Obstructive
PubMed: 35855746
DOI: 10.2147/COPD.S366126 -
International Journal of Chronic... 2023Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and... (Review)
Review
Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body's immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Lung; Exercise Therapy; Asthma; Respiration Disorders; Exercise Tolerance
PubMed: 37362621
DOI: 10.2147/COPD.S408325 -
Autopsy & Case Reports 2022Endobronchial lipomas are rare benign lung tumors that can cause bronchial obstruction and parenchymal damage. While an uncommon etiology, they are often misdiagnosed...
Endobronchial lipomas are rare benign lung tumors that can cause bronchial obstruction and parenchymal damage. While an uncommon etiology, they are often misdiagnosed due to a clinical presentation similar to obstructive pulmonary pathologies such as COPD and asthma. Upon review of English-language literature, under 50 cases of endobronchial lipomas were documented in the prior 10 years (2011-2021). There are no clear guidelines regarding the management of this particular entity, but typically interventional debulking is the treatment of choice. Here we present another unique case of endobronchial lipoma along with our diagnostic and therapeutic methodology. The patient underwent bronchoscopic debulking via a cryotherapy probe. Based on the histopathologic analysis, a diagnosis of endobronchial lipoma was made. Endobronchial lipomas must remain in any clinician's differential when a patient presents with dyspnea. We report the unique location of this lipoma based on our literature review and the importance of investigating endobronchial lesions due to a possible diagnosis of endobronchial lipoma.
PubMed: 35574045
DOI: 10.4322/acr.2021.377 -
American Journal of Respiratory and... Sep 2020Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk.... (Randomized Controlled Trial)
Randomized Controlled Trial
Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium. To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB. Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ). Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount ( < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; = 0.0002) and SGRQ (mean, -14.6; median, -7.2; = 0.0002) scores were observed, with similar observations through 12 months. This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).
Topics: Ablation Techniques; Aged; Bronchi; Bronchitis, Chronic; Disease Progression; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Prospective Studies; Quality of Life; Time Factors; Treatment Outcome
PubMed: 32407638
DOI: 10.1164/rccm.201908-1546OC -
Frontiers in Immunology 2020Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic... (Review)
Review
Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic inflammation, alveolar destruction (emphysema) and bronchiolar obstruction. Ozone is a gaseous constituent of urban air pollution resulting from photochemical interaction of air pollutants such as nitrogen oxide and organic compounds. While acute exposure to ozone induces airway hyperreactivity and neutrophilic inflammation, chronic ozone exposure in mice causes activation of oxidative pathways resulting in cell death and a chronic bronchial inflammation with emphysema, mimicking cigarette smoke-induced COPD. Therefore, the chronic exposure to ozone has become a model for studying COPD. We review recent data on mechanisms of ozone induced lung disease focusing on pathways causing chronic respiratory epithelial cell injury, cell death, alveolar destruction, and tissue remodeling associated with the development of chronic inflammation and AHR. The initial oxidant insult may result from direct effects on the integrity of membranes and organelles of exposed epithelial cells in the airways causing a stress response with the release of mitochondrial reactive oxygen species (ROS), DNA, and proteases. Mitochondrial ROS and mitochondrial DNA activate NLRP3 inflammasome and the DNA sensors cGAS and STING accelerating cell death pathways including caspases with inflammation enhancing alveolar septa destruction, remodeling, and fibrosis. Inhibitors of mitochondrial ROS, NLRP3 inflammasome, DNA sensor, cell death pathways, and IL-1 represent novel therapeutic targets for chronic airways diseases underlined by oxidative stress.
Topics: Air Pollutants; Air Pollution; Airway Remodeling; Animals; Anti-Inflammatory Agents; Antioxidants; Cell Death; Environmental Exposure; Humans; Inflammation Mediators; Lung; Oxidative Stress; Ozone; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Reactive Oxygen Species; Signal Transduction
PubMed: 32983127
DOI: 10.3389/fimmu.2020.01957 -
International Journal of Chronic... 2022Macrophage polarization plays an important role in the pathogenesis of COPD emphysema. Changes in macrophage polarization in COPD remain unclear, while polarization and...
BACKGROUND
Macrophage polarization plays an important role in the pathogenesis of COPD emphysema. Changes in macrophage polarization in COPD remain unclear, while polarization and ferroptosis are essential factors in its pathogenesis. Therefore, this study investigated the relationship between macrophage polarization and ferroptosis in COPD emphysema.
METHODS
We measured macrophage polarization and the levels of matrix metalloproteinases (MMPs) in the lung tissues of COPD patients and cigarette smoke (CS)-exposed mice. Flow cytometry was used to determine macrophage (THP-M cell) polarization changes. Ferroptosis was examined by FerroOrange, Perls' DAB, C11-BODIPY and 4-HNE staining. Nuclear receptor coactivator 4 (NCOA4) was measured in the lung tissues of COPD patients and CS-exposed mice by western blotting. A cell study was performed to confirm the regulatory effect of NCOA4 on macrophage polarization.
RESULTS
Increased M2 macrophages and MMP9 and MMP12 levels were observed in COPD patients, CS-exposed mice and THP-M cells cocultured with CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased NCOA4 levels and ferroptosis were confirmed in COPD. Treatment with NCOA4 siRNA and the ferroptosis inhibitor ferrostatin-1 revealed an association between ferroptosis and M2 macrophages. These findings support a role for NCOA4, which induces an increase in M2 macrophages, in the pathogenesis of COPD emphysema.
CONCLUSION
In our study, CS led to the dominance of the M2 phenotype in COPD. We identified NCOA4 as a regulator of M2 macrophages and emphysema by mediating ferroptosis, which offers a new direction for research into COPD diagnostics and treatment.
Topics: Animals; Disease Models, Animal; Emphysema; Epithelial Cells; Ferroptosis; Humans; Macrophages; Mice; Nuclear Receptor Coactivators; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Nicotiana
PubMed: 35386390
DOI: 10.2147/COPD.S354896 -
Journal of Thoracic Disease Aug 2021The clinical manifestations of foreign body (FB) aspiration can range from an asymptomatic presentation to a life-threatening emergency. Patients may present with acute... (Review)
Review
The clinical manifestations of foreign body (FB) aspiration can range from an asymptomatic presentation to a life-threatening emergency. Patients may present with acute onset cough, chest pain, breathlessness or sub-acutely with unexplained hemoptysis, non-resolving pneumonia and at times, as an incidental finding on imaging. Patients with iatrogenic FB such as an aspirated broken tooth during difficult intubation or a broken instrument are more common scenarios in the intensive care unit (ICU). Patients with post-obstructive pneumonia with or without sepsis, or variable degree of hemoptysis often require ICU level of care and bronchoscopic interventions. Rigid bronchoscopy has traditionally been the modality of choice; however, with the innovation in instrumentation and wider availability of flexible bronchoscopes, most of the FB removal is now successfully performed using flexible bronchoscopy. Proceduralists choose instruments in accordance with their training and expertise. We describe the use of most common instruments including forceps, balloon catheters, and baskets. Role of cryoprobe and LASER in FB removal is reviewed as well. In general, larger working channel bronchoscopes are preferred; however, smaller working channel bronchoscopes may be used in situations when the patients are intubated with a smaller diameter endotracheal or tracheostomy tubes. Large size FB are removed with the grasping tool, bronchoscope, and endotracheal or tracheostomy tube, requiring preparation to safely re-establish the airway. After FB removal, bronchoscopy is re-performed to identify any residual FB, assess any injury to the airway, suction post-obstructive secretions or pus, control any active bleeding and remove granulation tissue that may be obstructing the airway. Additional interventions like balloon dilatation may be required to dislodge an impacted FB or to maintain patency of bronchial lumen. If bronchoscopic methods fail, surgery may be required for retrieval of FB in symptomatic patients or to resect suppurative or necrotizing lung process. Multidisciplinary approach involving intensivists, surgeons, and anesthesiologists is the key to optimal patient outcomes.
PubMed: 34527356
DOI: 10.21037/jtd.2020.03.94 -
Journal of Thoracic Disease Nov 2016Although tracheal stenosis and bronchial stenosis are relatively rare in the pediatric population, they are both associated with significant morbidity and mortality.... (Review)
Review
Although tracheal stenosis and bronchial stenosis are relatively rare in the pediatric population, they are both associated with significant morbidity and mortality. While most cases of congenital tracheal stenosis in children present as complete tracheal rings (CTRs), other congenital tracheal obstructions are also encountered in clinical practice. In addition, acquired obstructive tracheal conditions stemming from endotracheal trauma or previous surgical interventions may occur. Many affected children also have associated cardiovascular malformations, further complicating their management. Optimal management of children with tracheal or bronchial stenoses requires comprehensive diagnostic evaluation and optimization prior to surgery. Slide tracheoplasty has been the operative intervention of choice in the treatment of the majority of these children.
PubMed: 28066618
DOI: 10.21037/jtd.2016.11.74 -
European Respiratory Review : An... Jun 2019Chronic obstructive pulmonary disease (COPD) is characterised by nonreversible proximal bronchial obstruction leading to major respiratory disability. However, patient... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is characterised by nonreversible proximal bronchial obstruction leading to major respiratory disability. However, patient phenotypes better capture the heterogeneously reported complaints and symptoms of COPD. Recent studies provided evidence that classical bronchial obstruction does not properly reflect respiratory disability, and symptoms now form the new paradigm for assessment of disease severity and guidance of therapeutic strategies. The aim of this review was to explore pathways addressing COPD pathogenesis beyond proximal bronchial obstruction and to highlight innovative and promising tools for phenotyping and bedside assessment. Distal small airways imaging allows quantitative characterisation of emphysema and functional air trapping. Micro-computed tomography and parametric response mapping suggest small airways disease precedes emphysema destruction. Small airways can be assessed functionally using nitrogen washout, probing ventilation at conductive or acinar levels, and forced oscillation technique. These tests may better correlate with respiratory symptoms and may well capture bronchodilation effects beyond proximal obstruction.Knowledge of inflammation-based processes has not provided well-identified targets so far, and eosinophils probably play a minor role. Adaptative immunity or specific small airways secretory protein may provide new therapeutic targets. Pulmonary vasculature is involved in emphysema through capillary loss, microvascular lesions or hypoxia-induced remodelling, thereby impacting respiratory disability.
Topics: Airway Remodeling; Animals; Disability Evaluation; Hemodynamics; Humans; Lung; Phenotype; Point-of-Care Testing; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiration; Respiratory Function Tests; Severity of Illness Index; Vascular Remodeling; X-Ray Microtomography
PubMed: 31285287
DOI: 10.1183/16000617.0010-2019