BACKGROUND: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. METHODS: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only 5x10(4) MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. RESULTS: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. CONCLUSION: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.
Airway Remodeling ; Animals ; Apoptosis ; Bronchitis, Chronic ; Emphysema ; Humans ; Lung ; Matrix Metalloproteinase 9 ; Mesenchymal Stromal Cells* ; Methods ; Mice ; Models, Animal ; Pancreatic Elastase* ; Pulmonary Disease, Chronic Obstructive ; Regeneration ; Stem Cells ; Tobacco Products ; Vascular Endothelial Growth Factor A

No abstract available.
Positive-Pressure Respiration, Intrinsic ; Airway Resistance ; Bronchitis, Chronic ; Lung Compliance ; Vena Cava, Inferior ; Work of Breathing ; Heart Ventricles ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive ; Lung ; Respiratory Muscles ; Pulmonary Emphysema ; Emphysema ; Pneumonia ; Cardiac Output ; Lung Transplantation ; Intensive Care Units ; Positive-Pressure Respiration ; Barotrauma ; Hypotension ; Korea

No abstract available.
Positive-Pressure Respiration, Intrinsic ; Airway Resistance ; Bronchitis, Chronic ; Lung Compliance ; Vena Cava, Inferior ; Work of Breathing ; Heart Ventricles ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive ; Lung ; Respiratory Muscles ; Pulmonary Emphysema ; Emphysema ; Pneumonia ; Cardiac Output ; Lung Transplantation ; Intensive Care Units ; Positive-Pressure Respiration ; Barotrauma ; Hypotension ; Korea

BACKGROUND: Chronic obstructive lung disease is characterized by smoke-related, gradually progressive, fixed airflow obstructions. However, some studies suggested that a reversible bronchial obstruction is common in chronic obstructive lung disease. Such reversibility persists despite the continued treatment with aerosolized bronchodilators and it appears to be related to the diminution in symptoms. The isolated volume response to a bronchodilator is defined as a remarkable increase in the FVC in response to the administration of a bronchodilator whereas the FEV1 remains unchanged. This has been suggested in patients with severe emphysema. Therefore, the aim of this study was to determine the relationship between the response to a bronchodilator and the severity of an airflow obstruction in COPD patients using the GOLD classification. METHODS: This study examined 124 patients with an airway obstruction. The patients underwent spirometry, and the severity of the airflow obstruction was classified by GOLD. The response groups were categorized by an improvement in the FVC or FEV1 > 12%, and each group was analyzed. RESULTS: Most subjects were men with a mean age of 65.9+/-8.5 years. The mean smoking history was 41.26+/-20.1 pack years. The isolated volume response group had relatively low FEV1 and FVC values compared with the other groups. (p<0.001) CONCLUSION: In this study, an isolated volume response to a bronchodilator is a characteristic of a severe airway obstruction, which is observed in patient with a relatively poorer baseline lung function.
Airway Obstruction ; Bronchodilator Agents ; Classification* ; Emphysema ; Humans ; Lung ; Male ; Pulmonary Disease, Chronic Obstructive* ; Smoke ; Smoking ; Spirometry

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characteristic of small airway inflammation, obstruction, and emphysema. It is well known that spirometry alone cannot differentiate each separate component. Computed tomography (CT) is widely used to determine the extent of emphysema and small airway involvement in COPD. Compared with the pulmonary function test, small airway CT phenotypes can accurately reflect disease severity in patients with COPD, which is conducive to improving the prognosis of this disease. CT measurement of central airway morphology has been applied in clinical, epidemiologic, and genetic investigations as an inference of the presence and severity of small airway disease. This review will focus on presenting the current knowledge and methodologies in chest CT that aid in identifying discrete COPD phenotypes.
Airway Obstruction ; Humans ; Phenotype ; Pulmonary Disease, Chronic Obstructive/diagnostic imaging* ; Pulmonary Emphysema/diagnostic imaging* ; Tomography, X-Ray Computed

Chronic obstructive pulmonary disease (COPD) is commonly a combination of pulmonary emphysema and chronic bronchitis. Emphysema is a pathologically defined disease that can be accurately diagnosed using CT. Furthermore, CT is useful for determination of the subtypes, extent and distribution of emphysema. Objective quantification of emphysema is feasible using CT densitometry of lung parenchyma, that can be used for selection of adequate candidates and monitoring clinical results of various therapeutic measures for severe emphysema. Imaging parameters in CT densitometry should be kept constant in follow up examination for an effective comparison of the results. Chronic bronchitis is diagnosed by symptomatic criteria with nonspecific CT findings. Airway dimensions can be objectively measured using CT, enabling further understanding of pathophysiology of COPD.
Bronchitis, Chronic ; Densitometry ; Emphysema ; Follow-Up Studies ; Lung ; Lung Diseases, Obstructive ; Pulmonary Disease, Chronic Obstructive ; Pulmonary Emphysema ; Thorax

BACKGROUND: The detection of collapsible airways has important therapeutic implications in chronic airway disease and bronchial asthma. The distinction of a purely collapsible airways disease from that of asthma is important because the treatment of the former may include the use of pursed lip breathing or nasal positive pressure ventilation whereas in the latter, pharmacologic approaches are used. One form of irreversible airflow limitation is collapsible airways, which has been shown to be a component of asthma or to emphysema, it can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmography. METHOD: To investigate whether volume difference between slow and forced vital capacity(SVC-FVC) by spirometry may be used as a surrogate index of airway collapse, we examined pulmonary function parameters before and after bronchodilator agent inhalation by spirometry and body plethysmography in 20 cases of patients with evidence of airflow limitation(chronic obstructive pulmonary disease 12 cases, stable bronchial asthma 7 cases, combined chronic obstructive pulmonary disease with asthma 1 case) and 20 cases of normal subjects without evidence of airflow limitation referred to the Pusan National University Hospital pulmonary function laboratory from January 1995 to July 1995 prospectively. RESULTS: 1) Average and standard deviation of age, height, weight of patients with airflow limitation was 58.3+/-7.24(yr), 166+/-8.0(cm), 59.0+/-9.9(kg) and those of normal subjects was 56.3+/-12.47(yr), 165.9+/-6.9(cm), 64.4+/-10.4(kg), respectively. The differences of physical characteristics of both group were not significant statistically and male to female ratio was 14:6 in both groups. 2) The difference between slow vital capacity and forced vital capacity was 395+/-317ml in patients group and 154+/-176ml in normal group and there was statistically significance between two groups(p<0.05). Sensitivity and specificity were most higher when the cut-off value was 208ml. 3) After bronchodilator inhalation, reversible airway obstructions were shown in 16 cases of patients group, 7 cases of control group(p<0.05) by spirometry or body plethysmography and the differences of slow vital capacity and forced vital capacity in bronchodilator response group and nonresponse group were 300.4+/-306ml, 144.7+/- 180ml and this difference was statistically significant. 4) The difference between slow vital capacity and forced vital capacity before bronchodilator inhalation was correlated with airway resistance before bronchodilator(r=0.307 p=0.05), and the difference between slow vital capacity and forced vital capacity after bronchodilator was correlated with difference between slow vital capacity and forced vital capacity(r=0.559 p=0.0002), thracic gas volume(r=0.488 p=0.002) before bronchodilator and airway resistance(r=0.583 p=0.0001), thoracic gas volume(r=0.375 p=0.0170) after bronchodilator, respectively. 5) The difference between slow vital capacity and forced vital capacity in smokers and nonsmokers was 267.5+/-303ml, 277.5+/-276ml, respectively and this difference did not reach statistical significance(p>0.05). CONCLUSION: The difference between slow vital capacity and forced vital capacity by spirometry may be useful for the detection of collapsible airway and may help decision making of therapeutic plans.
Airway Obstruction ; Airway Resistance ; Asthma ; Bronchodilator Agents ; Busan ; Decision Making ; Emphysema ; Female ; Humans ; Inhalation ; Lip ; Lung ; Lung Diseases, Obstructive ; Male ; Plethysmography ; Positive-Pressure Respiration ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; Respiration ; Sensitivity and Specificity ; Spirometry ; Vital Capacity

BACKGROUND: Smoking is the most important and consistent determinant of the development and progression of COPD(Ed Note : Define COPD). The fact that cigarette smokers develop a different type of COPD, chronic bronchitis and emphysema, with different clinical and pathological aspects, suggests that the development of COPD has a relationship with other smoking-associated factors beyoud just a simple smoking history. The aim of this was to analyze the smoking habits and history of patients with COPD and to evaluate the development of different types of COPD accordint to patient's smoking habits. METHOD: To evaluate the differences in the smoking patterens of patients with chronic bronchitis and emphysema, a pulmonary function test was conducted, and the smoking history and patterns was obtained through a smoking history questionnaire by a direct personal interview from 333 male cigarette smokers diagnosed with COPD, in the Yeungnam university medical center(190 patients diagnosed with chronic bronchitis, 143 patients diagnosed with emphysema). RESULT: The patients with emphysema smoked earlier and had a higher smoking history(ie, more pachyears, more total amounts of smoked cigarette, and more deep inhalation and longer duration of plain cigarette exposure) than those with chronic bronchitis. The depth of ingalation was also significantly higher in the emphysema patients after taking into account age, cumulative cagarette consumption and the type of cigarette smoked. CONCLUSION: Emphysema was more associated with the increasing degree of inhalation as assessed by the depth of inhalation. A high alveolar smoke exposure may be a significant risk factor for the development of emphysema.
Bronchitis, Chronic* ; Emphysema* ; Humans ; Inhalation ; Male ; Pulmonary Disease, Chronic Obstructive ; Respiratory Function Tests ; Risk Factors ; Smoke* ; Smoking* ; Tobacco Products

Chronic obstructive pulmonary disease (COPD) encompasses several clinical syndromes, most notably emphysema and chronic bronchitis. Most of the current treatments fail to attenuate severity and progression of the disease, thereby requiring better mechanistic understandings of pathogenesis to develop disease-modifying therapeutics. A number of theories on COPD pathogenesis have been promulgated wherein an increase in protease burden from chronic inflammation, exaggerated production of reactive oxygen species and the resulting oxidant injury, or superfluous cell death responses caused by enhanced cellular injury/damage were proposed as the culprit. These hypotheses are not mutually exclusive and together likely represent the multifaceted biological processes involved in COPD pathogenesis. Recent studies demonstrate that mitochondria are involved in innate immune signaling that plays important roles in cigarette smoke-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. These responses are reviewed herein and synthesized into a view of COPD pathogenesis whereby mitochondria play a central role.
Biological Processes ; Bronchitis, Chronic ; Cell Death ; Emphysema ; Inflammasomes ; Inflammation ; Mitochondria ; Pneumonia ; Pulmonary Disease, Chronic Obstructive* ; Reactive Oxygen Species ; Tobacco Products

PURPOSE: To determine the utility of HRCT in the diagnosis of chronic airflow obstruction and to correlate the morphologic abnormalities revealed by this modality with functional impairment in patients with chronic air-flow obstruction. MATERIALS AND METHODS:This study involved 80 patients with chronic airflow obstruction who underwent HRCT and a pulmonary function test. Final clinical diagnosis in these patients was determined by a chest physician on the basis of clinical features, bronchoscopy, pulmonary function test, and HRCT. In order to diagnose and determine the extent of areas of decreased attenuation revealed by HRCT (the CT score), the find-ings of HRCT were retrospectively reviewed by two radiologists, who reached a consensus. Clinical and HRCT diagnoses were then compared, and the rate of agreement between them was calculated. The relation-ship between the extent of areas of decreased attenuation revealed by HRCT and by FEV1/FVC was evaluated using Correl 's account and Student 's unpaired t-test. RESULTS: The agreement rate between clinical and HRCT diagnoses was 77.5% (62/80). The rates for bronchiec-tasis (88.9%, 24/27), emphysema (93.9%, 31/33), and bronchiolitis obliterans (100%, 6/6) were considerably higher than those for chronic bronchitis and bronchial asthma. The correlation rate between CT score and FEV1/FVC was significant in bronchiectasis (p<0.05; r: -0.76) and bronchiolitis obliterans (p<0.01; r:-0.66), but not in cases involving emphysema, bronchial asthma, or chronic bronchitis (p>0.05). CONCLUSION: HRCT is valuable in the diagnosis and prediction of physiologic impairment in patients with bronchiectasis and bronchiolitis obliterans, but has limited value in those with emphysema, chronic bronchitis or asthma.
Asthma ; Bronchiectasis ; Bronchiolitis Obliterans ; Bronchitis, Chronic ; Bronchoscopy ; Consensus ; Diagnosis* ; Emphysema ; Humans ; Pulmonary Disease, Chronic Obstructive* ; Pulmonary Emphysema ; Respiratory Function Tests* ; Retrospective Studies ; Thorax