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American Journal of Respiratory and... Aug 2022The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema...
The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired Dl, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. This statement delineates the syndrome of CPFE and highlights research priorities.
Topics: Emphysema; Female; Humans; Hypertension, Pulmonary; Lung; Lung Diseases, Interstitial; Male; Pulmonary Emphysema; Pulmonary Fibrosis; Retrospective Studies; Syndrome; Systematic Reviews as Topic
PubMed: 35969190
DOI: 10.1164/rccm.202206-1041ST -
Chinese Medical Journal Oct 2019Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease of human beings characterized by not fully reversible airflow limitation. Emphysema... (Review)
Review
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease of human beings characterized by not fully reversible airflow limitation. Emphysema is the main pathological feature of COPD which causes high mortality worldwide every year and consumes a large amount of medical expenses. This paper was to review the establishment and evaluation methods of animal models of emphysema or COPD, and put forward some new ideas on animal selection, method of modeling, and model evaluation.
DATA SOURCES
The author retrieved information from the PubMed database up to July 2019, using various combinations of search terms, including emphysema, model, and animal.
STUDY SELECTION
Original articles, reviews, and other articles were searched and reviewed for animal models of emphysema.
RESULTS
This review summarized animal models of emphysema from the perspectives of animal selection, emphysema mechanism, modeling method and model evaluation, and found that passive smoking is the classic method for developing animal model of emphysema, mice are more suitable for experimental study on emphysema. Compared with pulmonary function indicators, airway inflammation indicators and oxidative stress indicators, pathomorphological indicators of lung tissue are the most important parameters for evaluating the establishment of the animal model of emphysema.
CONCLUSIONS
Mice model induced by passive smoking is the classic animal model of emphysema. Pathomorphological indicators are the most important parameters for evaluating the establishment of the animal model of emphysema.
Topics: Animals; Disease Models, Animal; Humans; Inflammation; Pancreatic Elastase; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Nicotiana; Tobacco Smoke Pollution; Vagus Nerve Stimulation
PubMed: 31567388
DOI: 10.1097/CM9.0000000000000469 -
International Journal of Chronic... 2021Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent... (Review)
Review
BACKGROUND
Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients.
OBJECTIVE
Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE.
METHODS
We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data.
RESULTS
Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers.
CONCLUSION
CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients.
Topics: Animals; Emphysema; Female; Humans; Idiopathic Pulmonary Fibrosis; Lung Neoplasms; Male; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies
PubMed: 33536752
DOI: 10.2147/COPD.S286360 -
International Journal of Chronic... 2015Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully... (Review)
Review
Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet. We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade. Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke. The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied. However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between. Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays.
Topics: Airway Remodeling; Animals; Autoimmunity; Dysbiosis; Environment; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Inflammation Mediators; Lung; Microbiota; Oxidative Stress; Prognosis; Proteolysis; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Reactive Oxygen Species; Regeneration; Risk Factors; Signal Transduction
PubMed: 26082624
DOI: 10.2147/COPD.S82518 -
American Journal of Physiology. Lung... Nov 2020
Topics: Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema
PubMed: 33050739
DOI: 10.1152/ajplung.00473.2020 -
Physiological Reviews Apr 2023The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the... (Review)
Review
The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why emphysema progresses in a subset of former smokers remained a mystery for many years. The recognition of activated and organized tertiary T- and B-lymphoid aggregates in emphysematous lungs provided the first clue that adaptive immune cells may play a crucial role in COPD pathophysiology. Based on these findings from human translational studies, experimental animal models of emphysema were used to determine the mechanisms through which smoke exposure initiates and orchestrates adaptive autoreactive inflammation in the lungs. These models have revealed that T helper (Th)1 and Th17 subsets promote a positive feedback loop that activates innate immune cells, confirming their role in emphysema pathogenesis. Results from genetic studies and immune-based discoveries have further provided strong evidence for autoimmunity induction in smokers with emphysema. These new findings offer a novel opportunity to explore the mechanisms underlying the inflammatory landscape in the COPD lung and offer insights for development of precision-based treatment to halt lung destruction.
Topics: Animals; Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema; Lung; Adaptive Immunity; Models, Theoretical
PubMed: 36201635
DOI: 10.1152/physrev.00036.2021 -
Thorax Nov 2023Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised...
BACKGROUND
Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations.
METHODS
New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined.
RESULTS
The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near , which is implicated in mucin hypersecretion (p=1.1 ×10). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome.
CONCLUSION
Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.
Topics: Humans; Pulmonary Emphysema; Case-Control Studies; Unsupervised Machine Learning; Pulmonary Disease, Chronic Obstructive; Lung; Emphysema; Tomography, X-Ray Computed
PubMed: 37268414
DOI: 10.1136/thorax-2022-219158 -
Respiratory Research Mar 2019Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse... (Review)
Review
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathological changes are not complete. In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation. We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations. We discuss the need to specifically target SAD to attenuate the progression of COPD.
Topics: Airway Remodeling; Animals; Disease Progression; Forecasting; Humans; Inflammation; Lung; Mucus; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Smoking
PubMed: 30832670
DOI: 10.1186/s12931-019-1017-y -
The Journal of Pathology Apr 2020Chronic obstructive pulmonary disease (COPD) is a devastating lung disease with a high personal and societal burden. Exposure to toxic particles and gases, including... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is a devastating lung disease with a high personal and societal burden. Exposure to toxic particles and gases, including cigarette smoke, is the main risk factor for COPD. Together with smoking cessation, current treatment strategies of COPD aim to improve symptoms and prevent exacerbations, but there is no disease-modifying treatment. The biggest drawback of today's COPD treatment regimen is the 'one size fits all' pharmacological intervention, mainly based on disease severity and symptoms and not the individual's disease pathology. To halt the worrying increase in the burden of COPD, disease management needs to be advanced with a focus on personalized treatment. The main pathological feature of COPD includes a chronic and abnormal inflammatory response within the lungs, which results in airway and alveolar changes in the lung as reflected by (small) airways disease and emphysema. Here we discuss recent developments related to the abnormal inflammatory response, ECM and age-related changes, structural changes in the small airways and the role of sex-related differences, which are all relevant to explain the individual differences in the disease pathology of COPD and improve disease endotyping. Furthermore, we will discuss the most recent developments of new treatment strategies using biologicals to target specific pathological features or disease endotypes of COPD. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Topics: Humans; Lung; Lung Diseases; Precision Medicine; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Nicotiana
PubMed: 31691283
DOI: 10.1002/path.5364 -
Cells Jun 2022Alveolar type II (ATII) cells are progenitors in alveoli and can repair the alveolar epithelium after injury. They are intertwined with the microenvironment for alveolar... (Review)
Review
Alveolar type II (ATII) cells are progenitors in alveoli and can repair the alveolar epithelium after injury. They are intertwined with the microenvironment for alveolar epithelial cell homeostasis and re-epithelialization. A variety of ATII cell niches, transcription factors, mediators, and signaling pathways constitute a specific environment to regulate ATII cell function. Particularly, WNT/β-catenin, YAP/TAZ, NOTCH, TGF-β, and P53 signaling pathways are dynamically involved in ATII cell proliferation and differentiation, although there are still plenty of unknowns regarding the mechanism. However, an imbalance of alveolar cell death and proliferation was observed in patients with pulmonary emphysema, contributing to alveolar wall destruction and impaired gas exchange. Cigarette smoking causes oxidative stress and is the primary cause of this disease development. Aberrant inflammatory and oxidative stress responses result in loss of cell homeostasis and ATII cell dysfunction in emphysema. Here, we discuss the current understanding of alveolar re-epithelialization and altered reparative responses in the pathophysiology of this disease. Current therapeutics and emerging treatments, including cell therapies in clinical trials, are addressed as well.
Topics: Alveolar Epithelial Cells; Humans; Lung; Pulmonary Alveoli; Pulmonary Emphysema; Re-Epithelialization
PubMed: 35805139
DOI: 10.3390/cells11132055