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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 -
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... 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 -
BMJ (Clinical Research Ed.) Nov 1994
Topics: Humans; Lung; Pulmonary Emphysema; Smoking
PubMed: 7888832
DOI: 10.1136/bmj.309.6964.1244 -
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 -
Cells Apr 2023Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis... (Review)
Review
Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.
Topics: Male; Humans; Pulmonary Fibrosis; Pulmonary Emphysema; Lung; Hypertension, Pulmonary; Emphysema
PubMed: 37174678
DOI: 10.3390/cells12091278 -
European Respiratory Review : An... Mar 2023COPD and α-1 antitrypsin deficiency emphysema remain one of the major indications for lung transplantation. If all other treatment possibilities are exhausted or not...
COPD and α-1 antitrypsin deficiency emphysema remain one of the major indications for lung transplantation. If all other treatment possibilities are exhausted or not possible (including rehabilitation, oxygen therapy, noninvasive ventilation, lung volume reduction), patients may qualify for lung transplantation. Strict selection criteria are implemented with a lot of relative and absolute contraindications. Because of an ongoing donor shortage, only a minority of endstage COPD patients will finally get transplanted. The procedure may involve a single or a double lung transplantation, dependent on the experience of the centre, the waiting list, the availability of donor lungs and the patient's risk-benefit ratio. In general, the life expectancy as well as the health-related quality of life after lung transplantation for COPD are usually increased, and may be somewhat better after double compared with single lung transplantation. Several specific complications can be encountered, such as the development of solid organ cancer and chronic lung allograft dysfunction, which develops in up to 50% of patients within 5 years of their transplant and has a major impact on long-term survival, because of the current inefficient treatment modalities.
Topics: Humans; Pulmonary Emphysema; Quality of Life; Lung Transplantation; Lung; alpha 1-Antitrypsin Deficiency
PubMed: 36948499
DOI: 10.1183/16000617.0116-2022 -
Medicina (Kaunas, Lithuania) Sep 2019Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10-15 years as a clinical entity characterized by rather severe imaging... (Review)
Review
Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10-15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process. The outcome of combined emphysema and fibrosis results in higher lung volumes overall on PFTs compared to patients with pulmonary fibrosis alone, and the forced expiratory volume in one second (FEV)/forced vital capacity (FVC) ratio in CPFE patients is generally preserved despite the presence of emphysema on chest computed tomography (CT) imaging. Conversely, there appears to be an additive deleterious effect on gas exchange properties of the lungs, reflecting a loss of normally functioning alveolar capillary units and effective surface area available for gas exchange, and manifested by a uniformly observed severe reduction in the diffusing capacity for carbon monoxide (DCO). Despite normal or only mildly impaired spirometric and lung volume indices, patients with CPFE are often severely functionally impaired with an overall rather poor prognosis. As chest CT imaging continues to be a frequent imaging modality in patients with cardiopulmonary disease, we expect that patients with a combination of pulmonary emphysema and pulmonary fibrosis will continue to be observed. Understanding the pathophysiology of this combined process and the abnormalities that manifest on PFT testing will likely be helpful to clinicians involved with the care of patients with CPFE.
Topics: Humans; Pulmonary Emphysema; Pulmonary Fibrosis; Respiratory Function Tests
PubMed: 31509942
DOI: 10.3390/medicina55090580