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Sarcoidosis is a systemic disease of unknown etiology characterized by the formation of noncaseating granulomas.Its clinical manifestations are heterogeneous,and the determinants of clinical course(such as active vs inac-tive,remission vs chronic progression,and fibrosis vs non-fibrosis)are poorly understood.Despite considerable effort over many years,the exact pathogenesis of sarcoidosis has not been fully elucidated.Animal models have made significant con-tributions to understanding the etiology and the development of this disease.In this review,we presented the clinical rele-vance of animal models in sarcoidosis,summarized the methods for constructing the models,and discussed how they have strengthened our understanding of sarcoidosis.
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BACKGROUND@#The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.@*METHODS@#In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.@*RESULTS@#A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.@*CONCLUSIONS@#Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
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Humans , Bronchoalveolar Lavage Fluid , Prospective Studies , Alveolitis, Extrinsic Allergic/diagnosis , Fibrosis , CarbohydratesABSTRACT
Objective To probe into the total number and development status of respiratory physicians in China, and to analyze existing problems, for reference in making strategy and policy decisions in professional development of respiratory physicians in the country. Methods The basic information of China′s healthcare institutions and healthcare manpower in 2015 were provided by the Statistics Center of the National Health Commission. The number of respiratory specialists and their profile, drawn from such basic information, were subject to descriptive statistics. Results In 2015, there were 2.729 million medical practitioners ( including assistant doctors ) nationwide, 30.3 thousand among whom being respiratory physicians, accounting for 1.11% of the total. Among these respiratory physicians, practicing respiratory physicians account for 87.1% , respiratory physicians with a master degree and above account for only 19.7% , respiratory physicians with over 10 years of working experience account for 65.8% , respiratory physicians with senior titles account for only 21.4% , and 89.4% of the respiratory physicians work in general hospitals. Conclusions By the criteria of specializing in respiratory specialty over five years and being attending or above, the number approximates 14. 6 thousand nationwide. If practicing ( assistant) physicians specializing in respiratory specialty are also included, the number may hit 30. 3 thousand. Such a number, compared with other specialties, may be sufficient, yet their competence is far from satisfactory. Therefore it is imperative to build a standardized pulmonary medicine fellowship training system for their competence improvement.
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Objective To learn the present setup of respiratory departments as well as development of diagnosis and treatment in China, for reference and policy making of the respiratory specialty development. Methods In May and June 2016,3 202 hospitals were surveyed, to learn their respiratory department development,development of sub-specialty,naming of departments,staffing ratio of the medical staff to bed,basic indicators for medical services,medical techniques and disease types treated. Results 77.8% of the tertiary hospitals and 38.8% of the secondary hospitals have independent respiratory departments. Among such tertiary hospitals,54.4% of them have respiratory intensive care units,21.8% have respiratory & sleep disorder clinics, and 13.1% have smoking cessation clinic. The physician-nurse ratio of respiratory department of such hospitals amounted to 1:1.66, while that of secondary hospitals to 1:1.61. 99.8% of the tertiary hospitals and about 95.0% of the secondary hospitals are competent of invasive positive pressure ventilation,noninvasive mechanical ventilation,and pulmonary function test among others. Conclusions Rooms of improvement are found in the following areas. Poor respiratory specialty and sub-specialty construction at such hospitals; insufficient nursing staff; tertiary hospitals have not formed unique advantages in diagnosis and treatment techniques and types of diseases; hierarchical medical system is to be further established.
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<p><b>BACKGROUND</b>Combined emphysema and pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), is a distinct disorder described with upper-lobe emphysema and lower-lobe fibrosis on chest computed tomography. Smoking appears to be the predominant risk factor for this disorder. We aimed to compare clinical features, smoking history, physiological and radiological findings between IPF with and without emphysema.</p><p><b>METHODS</b>A sample of 125 IPF patients over a period of 48 months were evaluated. High resolution CT scans were reviewed blinded to clinical data. The IPF patients with or without emphysema were classified accordingly.</p><p><b>RESULTS</b>The prevalence of emphysema in this IPF sample was 70/125. IPF with emphysema was significantly associated with smoking status (OR 63; 95% CI 4.4 to 915; P = 0.002) and smoking pack year (OR 1.1; 95% CI 1.05 to 1.13; P = 0.000). The patients with IPF and emphysema had a higher decrease in carbon monoxide diffusing capacity adjusted for alveolar volume ((58±19)% pred vs. (66±21)% pred; P = 0.021) and a higher prevalence of pulmonary hypertension (24/70 vs. 7/55; P = 0.006). The two groups of patients had similar forced and residual volumes. No significant differences were found in cell differentials of bronchoalveolar lavage or the scores of fibrosis on chest CT. Survival of the patients with emphysema was significantly less than that of patients with IPF alone.</p><p><b>CONCLUSIONS</b>Cigarette smoking induces IPF combined with emphysema. Emphysema further impairs physiological function and increases the prevalence of pulmonary hypertension that leads to poor prognosis. The inclusion of the patients with combined pulmonary fibrosis and emphysema in IPF clinical trials may lead to under evaluation of the effect of treatment in patients.</p>
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Aged , Female , Humans , Male , Middle Aged , Idiopathic Pulmonary Fibrosis , Pulmonary Emphysema , SmokingABSTRACT
<p><b>BACKGROUND</b>Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic. There is no effective therapy except for lung transplantation. Rapamycin is an immunosuppressive drug with potent antifibrotic activity. The purpose of this study was to examine the effects of rapamycin on bleomycin-induced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).</p><p><b>METHODS</b>Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model. Rapamycin was given at a dose of 0.5 mg/kg per gavage, beginning one day before bleomycin instillation and once daily until animal sacrifice. Ten rats in each group were sacrificed at 3, 7, 14, 28 and 56 days after bleomycin administration. Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System. Type I and III collagen fibers were identified by Picro-sirius-polarization. Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay, MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin. Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days. The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P < 0.05). It was also demonstrated that rapamycin treatment reduced the expression of MMP-9 and TIMP-1 in lung tissue that was increased by bleomycin.</p><p><b>CONCLUSION</b>These results highlight the significance of rapamycin in alleviating alveolitis and pulmonary fibrosis, which is associated with decreased expression of MMP-9 and TIMP-1.</p>
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Animals , Male , Rats , Bleomycin , Pharmacology , Lung , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Pulmonary Fibrosis , Drug Therapy , Rats, Sprague-Dawley , Sirolimus , Therapeutic Uses , Tissue Inhibitor of Metalloproteinase-1 , MetabolismABSTRACT
<p><b>BACKGROUND</b>Idiopathic pulmonary fibrosis (IPF) is a lethal chronic interstitial lung disease (ILD) of unknown cause and having a variable and unpredictable course. This study aimed to summarize the clinical features and follow-up outcomes and to identify potential factors useful for the assessment of prognosis in IPF.</p><p><b>METHODS</b>Two hundred and ten patients hospitalized and diagnosed as IPF in our unit from January 1999 to June 2007 were enrolled into this study. The baseline demographic, clinical, radiologic and physiologic characteristics were summarized. Clinical follow-up data until February 2010 were collected, and the median survival time and 1-, 2-, and 5-year survival rates, as well as the influences of the summarized baseline variables on the prognosis were analyzed.</p><p><b>RESULTS</b>The age at diagnosis as IPF was (64 ± 10) years, the duration before diagnosis of 106 patients (50%) was shorter than 2 years, and 73% were males. One hundred and forty-five patients (69%) had a history of smoking with a median pack-year of 18. Eighty-nine patients (42%) had emphysema and 62 patients (29%) pulmonary arterial hypertension (PAH). One hundred and twenty-four patients were followed up, of which 99 patients died from various causes including respiratory failure related to IPF (93%). The follow-up period was (21 ± 23) months. The median survival time was 38 months. The 1-, 2-, and 5-year survival rates were 61%, 52%, and 39%, respectively. Multivariate analysis showed clubbing, PAH, duration from initial onset to diagnosis, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) were independent prognostic indicators of IPF.</p><p><b>CONCLUSION</b>IPF patients who have clubbing, PAH, a higher FEV1/FVC, and a short duration from initial onset to diagnosis have a poorer outcome.</p>
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Aged , Female , Humans , Male , Middle Aged , Emphysema , Diagnosis , Mortality , Hypertension, Pulmonary , Diagnosis , Pathology , Idiopathic Pulmonary Fibrosis , Diagnosis , MortalityABSTRACT
<p><b>OBJECTIVE</b>To discuss the rationale, hypothesis, modality of extracorporeal blood purification (EBP) techniques for the critically ill animal models or patients, and to summarize the experimental and clinical studies with inconsistent data which explored the EBP's efficacy in the areas of critical care medicine.</p><p><b>DATA SOURCES</b>Articles referred in this review were collected from the database of PubMed published in English up to June 2014.</p><p><b>STUDY SELECTION</b>We had done a literature search by using the term "(sepsis OR acute lung injury OR acute respiratory distress syndrome) AND (extracorporeal blood purification OR hemofiltration OR hemoperfusion OR plasma exchange OR plasmapheresis OR adsorpiton)". Related original or review articles were included and carefully analyzed.</p><p><b>RESULTS</b>Acute cellular and humoral immune disturbances occur in both sepsis and acute respiratory distress syndrome (ARDS). Treatments aimed at targeting one single pro-/anti-inflammatory mediator have largely failed with no proven clinical benefits. Such failure shifts the therapeutic rationale to the nonspecific, broad-spectrum methods for modulating the over-activated inflammatory and anti-inflammatory response. Therefore, EBP techniques have become the potential weapons with high promise for removing the circulating pro-/anti-inflammatory mediators and promoting immune reconstitution. Over the years, multiple extracorporeal techniques for the critically ill animal models or patients have been developed, including hemofiltration (HF), high-volume hemofiltration (HVHF), high-cutoff hemofiltration (HCO-HF), hemo-perfusion or -adsorption (HP/HA), coupled plasma filtration adsorption (CPFA), and plasma exchange (PE). These previous studies showed that EBP therapy was feasible and safe for the critically ill animal models or patients. However, data on their efficacy (especially on the clinical benefits, such as mortality) were inconsistent.</p><p><b>CONCLUSIONS</b>It is not now to conclude that EBP intervention can purify septic or ARDS patients with high clinical efficacy from current experimental and clinical practice. Prospective, randomized controlled, and well-designed clinical or experimental studies and most suitable EBP modalities should be further developed.</p>
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Humans , Hemofiltration , Respiratory Distress Syndrome , Therapeutics , Sepsis , TherapeuticsABSTRACT
PURPOSE: The present study was designed to determine whether rapamycin could inhibit transforming growth factor beta1 (TGF-beta1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. MATERIALS AND METHODS: Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax. Growth arrested, synchronized fibroblasts were treated with TGF-beta1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay. RESULTS: Rapamycin significantly reduced TGF-beta1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-beta1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-beta1-mediated fibrogenic response in primary human lung fibroblasts. CONCLUSION: These results indicate that rapamycin effectively suppresses TGF-beta1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis.
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Humans , Cells, Cultured , Collagen Type III/metabolism , Fibroblasts/drug effects , Fibronectins/metabolism , Lung/cytology , Pulmonary Fibrosis/drug therapy , Signal Transduction/drug effects , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism , Transforming Growth Factor beta1/antagonists & inhibitorsABSTRACT
ObjectiveTo discuss the clinical experience and influence factors of airway complications after lung transplantation for end-stage lung diseases through reviewed 28 lung transplantation cases in our center.MethodsFrom August 2005 to December 2010,28 patients with end-stage lung diseases received lung transplantations consecutively in our center,in which 13 patients were bilateral-lung transplantation(BLT) and 15 patients were single-lung transplantation(SLT).The donor lungs were perfused with LPD solution antegrade and retrograde followed.During operation,the pulmonary artery pressure and flow rate were tested real time through the transesophageal echocardiography and Swans catheter.Postoperative care of patients was in respiratory intensive care unit,and immunosuppressive drugs were adjusted according to blood drug concentration.ResultsThere were no airway complications including anastomotic fistula or stenosis found in all patients.The mortality was 7.2% in the early postoperative period ( 1-30 days).Cumulative survival rate was 94.1% % at 1 year,76.2% at 2 years,and 71.4% at 3 years respectively.Four patients (14.3%) died in the postoperative 90 days.Three patients were reanastomosed pulmonary artery in operation because of stenosis detected by transesophageal echocardiography.After operation,three patients were reoperated,in which two were bleeding and one was pulmonary bulla and pneumothorax.All patients were followed from 1 year to 6.1 years after operation.The quality of life was improved significantly.ConclusionThe well improved technique of lung transplantation is helpful to reduce the operation related complications,decrease the early mortality post operation and play the important role in the effects of quality of life and long term survival rate.The intraoperative transesophageal echocardiography examination could detect the anomalous situation of vascular anastomosis.At the same time the patients should get benefits from the routine and close follow-up.
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Objective To investigate the clinical value of transesophageal echocardiography during the lung transplanta tion. Methods From August 2005 to August 2009, 19 patients with advanced lung diseases received lung transplantation.The average age was(48.35±13.04) years. The echocardiographic probe was placed in patient's esophagus before surgery.The left and right pulmonary venous openings, artery blood flow velocity, right ventricular wall motion, left and right ventricular volume, right ventricular ejection fraction were recorded at different time intervals during lung transplantation, especially at the break and after completion of bronchus, pulmonary veins, and pulmonary artery anastomosis. Results The procedure included sequential-type lung transplantation in 6 cases and single lung transplantation in 13. The blood flow disappeared when blocking pulmonary artery and vein and right ventricular volume increased slightly. The right ventricular volume restored after completion of trachea, pulmonary veins, pulmonary artery anastomosis. TEE detected that the blood flow velocity of pulmonary veins, pulmonay artery anastomosis increased slightly. In 1 case the opening of the right pulmonsry artery blood flow velocity increased significantly and blood flow velocity decresed and blood oxygen partial pressure resumed after re-anastomosis of pulmonary artery. Conclusion TEE play an important role in monitoring pulmonary artery and vein anastomosis diameter and blood flow velocity and right ventricular function and predicting complications during lung transplantation.
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Objective To determine the prevalence of gastroesophageal reflux disease (GERD) in patients with idiopathic pulmonary interstitial fibrosis (IPIF). Methods From December 2006 to January 2008, 24 consecutive patients with IPIF admitted to Beijing Chaoyang Hospital underwent 24-hour esophageal pH monitoring and esophageal manometry. Meanwhile, 23 patients with diffuse parenchymal lung disease (DPLD) (excluding IPIF) admired to the hospital in the same period served as a control group. Comparison of the prevalence of pathologic esophageal acid exposure GERD symptoms, and ineffective esophageal motility (IEM) between the two groups was made. In this study, nocturnal acid exposure is defined as acid reflux episodes occurring from 10pro to 6am. Results (1) 16 out of the 24 (66. 7%) patients with IPIF were demonstrated to have pathologic esophageal acid exposure; the prevalence of GERD in IPIF patients was significantly higher than that in other DPLD patients, whose prevalence was 26. 1% (P<0.05); (2) 87.5% patients with IPIF and GERD (GERD-IPIF) had nocturnal acid exposure episodes; (3) only 37.5% of the GERD-IPIF patients was found to have typical GERD symptoms such as heartburn and regurgitation; (4) The prevalence of IEM was similar in IPIF and other DPLD patients, being 42.9% and 39. 1% respectively (P >0. 05). Conclusions IPIF patients have higher prevalence of GERD and most of them usually do not show typical reflux symptoms. It is hereby suggested that IPIF patients should be screened with pH monitoring for GERD.
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After the tissue injuries appear,bone marrow mesenohymal stem cells(MSCs)migrate to the lesion place against the chemokine concentration gradient and produce natural compensatory repair by differentiation of the injured cells,immunological regulation and paracrine of various cytokines,such as hepatocyte growth factor(HGF).HGF is one of the important chemokine factors of MSCs.It can inhibit proliferation of MSCs and induce MSCs into hepatocytes and epithelial cells.However,the mechanisms of MSCs on the injured tissue repairing are complicated,and the underlying mechanism consists of homing to the injured lesion,correct oriented differentiation of local micrcenvironment and in inhibition on the host immunity.With the deeperresearch,the mechanism of reparative process MSCs acting on damaged tissue will be elucidated gradually.It may be helpful for the instruction of the clinical treatment to engraft MSCs which are modified with effective genes and to enhance the ability of ceil engraftment.
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<p><b>OBJECTIVE</b>To estimate the feasibility and the efficacy of early extubation and sequential non-invasive mechanical ventilation (MV) in chronic obstructive pulmonary disease (COPD) with exacerbated hypercapnic respiratory failure.</p><p><b>METHODS</b>Twenty-two intubated COPD patients with severe hypercapnic respiratory failure due to pulmonary infection (pneumonia or purulent bronchitis) were involved in the study. At the time of pulmonary infection control window (PIC window) appeared, when pulmonary infection had been significantly controlled (resolution of fever and decrease in purulent sputum, radiographic infiltrations, and leukocytosis) after the antibiotic and the comprehensive therapy, the early extubation was conducted and followed by non-invasive MV via facial mask immediately in 11 cases (study group). Other 11 COPD cases with similar clinical characteristics who continuously received invasive MV after PIC window were recruited as control group.</p><p><b>RESULTS</b>All patients had similar clinical characteristics and gas exchange before treatment, as well as the initiating time and all indices at the time of the PIC window. For study group and control group, the duration of invasive MV was (7.1 +/- 2.9) vs (23.0 +/- 14.0) days, respectively, P < 0.01. The total duration of ventilatory support was (13 +/- 7) vs (23 +/- 14) days, respectively, P < 0.05. The incidence of ventilator associated pneumonia (VAP) were 0/11 vs 6/11, respectively, P < 0.01. The duration of intensive care unit (ICU) stay was (13 +/- 7) vs (26 +/- 14) days, respectively, P < 0.05.</p><p><b>CONCLUSIONS</b>In COPD patients requiring intubation and MV for pulmonary infection and hypercapnic respiratory failure, early extubation followed by non-invasive MV initiated at the point of PIC window significantly decreases the invasive and total durations of ventilatory support, the risk of VAP, and the duration of ICU stay.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Hypercapnia , Therapeutics , Pulmonary Disease, Chronic Obstructive , Respiration, Artificial , Methods , Respiratory Insufficiency , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes in respiratory and circulatory functions in chronic obstructive pulmonary disease (COPD) patients during sequential invasive-noninvasive mechanical ventilation therapy, and evaluate the effects of this new technique.</p><p><b>METHODS</b>Twelve COPD patients with type II respiratory failure due to severe pulmonary infection were ventilated through an endotracheal tube. When the pulmonary infection control window (PIC-Window) occurred, the patients were extubated and were ventilated with a facial mask using pressure support ventilation combined with positive end-expiratory pressure. The parameters of hemodynamics, oxygen dynamics, and esophageal pressure were measured at the PIC-Window during invasive mechanical ventilation, one hour after oxygen therapy via a naso-tube, and three hours after non-invasive mechanical ventilation.</p><p><b>RESULTS</b>The variation in esophageal pressure was 20.0 +/- 6 cmH(2)O during naso-tube oxygen therapy, and this variation was higher than that during non-invasive mechanical ventilation (10 +/- 6 cmH(2)O, P < 0.01). The changes in respiratory and circulatory parameters were not significantly different between invasive mechanical ventilation and noninvasive mechanical ventilation (P > 0.05).</p><p><b>CONCLUSIONS</b>The respiratory and circulatory functions of COPD patients remained stable during sequential invasive-noninvasive mechanical ventilation therapy using PIC-Window as a switch point for early extubation. The COPD patients can tolerated the transition from invasive mechanical ventilation to noninvasive mechanical ventilation.</p>