OBJECTIVETo 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.

METHODSTwenty-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.

RESULTSAll 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.

CONCLUSIONSIn 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.

Adult ; Aged ; Female ; Humans ; Hypercapnia ; therapy ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; complications ; Respiration, Artificial ; methods ; Respiratory Insufficiency ; therapy

Humans ; Noninvasive Ventilation ; Cannula ; Airway Extubation ; Retrospective Studies ; Pulmonary Disease, Chronic Obstructive/therapy* ; Hypercapnia/therapy* ; Oxygen Inhalation Therapy ; Respiratory Insufficiency/therapy*

OBJECTIVETo study the effects of puerarin on pulmonary Vascular remodeling in rats with pulmonary hypertension induced by chronic hypoxia and hypercapnia.

METHODForty male rats (180-220) g of grade two were randomly divided into five groups: normal control group (NC), hypoxia-hypercapnia 1, 2, 3 week groups (LH1, LH2, LH3) and hypoxia-hypercapnia 3-week + puerarin group (LHP3 group, puerarin intraperitoneal injection, 20 mg x kg(-1) x d(-1)). Collagen I, III and their mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization.

RESULTLight microscopy showed media thickness of pulmonary arterioles was much higher in LH3 group than that of NC group, and, vessel cavity turned more straiter in LH3 group than that of NC group. Howerer, the damage of pulmonary arterioles in LHP3 group was much slighter than that of LH3 group. The levels of plasma ET-1 and lung homogenates Hyr and MDA were much higher in rats of LH3 group than those of NC group (P < 0.01), and lower in LHP3 group than LH3 groups (P < 0.01). The activities of SOD in lung homogenates were significantly lowered in hypoxic and hypercapnic groups compared with control group (P < 0.01), but higher in LHP3 group than that of LH3 group. Plasma NO content of group LH was lower than that of group NC (P < 0.01), it was highter in group LHP3 than that of group LH3 (P < 0.01). Expression of collagen I and collagen I mRNA in pulmonary arterioles were significantly higher in rats of LH groups than those of NC group (P < 0.01), and they were lower in rats of LHP3 group than those of LH3 group (P < 0. 01). Expression of collagen III and collagen III mRNA were not significant difference among three groups.

CONCLUSIONPuerarin could improve pulmonary vascular remodeling in rats with pulmonary hypertension by inhibiting the deposition of collagen.

Animals ; Hypercapnia ; complications ; Hypertension, Pulmonary ; drug therapy ; Hypoxia ; complications ; Isoflavones ; pharmacology ; Male ; Oxidative Stress ; drug effects ; Pulmonary Artery ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Community-acquired pneumonia (CAP) remains a common and serious condition worldwide. The mortality from severe CAP remains high, and this has reached 50% in some series. This study was conducted to determine the mortality and predictors that contribute to in-hospital mortality for patients who exhibit CAP and acute respiratory failure that requires mechanical ventilation. METHODS: We retrospectively reviewed the medical records of 85 patients with severe CAP as a primary cause of acute respiratory failure, and this required mechanical ventilation in a setting of the medical intensive care unit (ICU) of a tertiary university hospital between 2000 and 2003. RESULTS: The overall in-hospital mortality was 56% (48/85). A Cox-proportional hazard model revealed that the independent predictive factors of in-hospital mortality included a PaCO2 of less than 45 mmHg (p<0.001, relative risk [RR]: 4.73; 95% confidence interval [CI]: 2.16-10.33), a first 24-hour urine output of less than 1.5 L (p=0.006, RR: 2.46, 95% CI: 1.29-4.66) and a high APACHE II score (p=0.004, RR: 1.09, 95% CI: 1.03-1.16). CONCLUSIONS: Acute respiratory failure caused by severe CAP and that necessitates mechanical ventilation is associated with a high mortality rate. Initial hypercapnia and a large urine output favored survival, whereas a high APACHE II score predicted mortality.
Aged ; Aged, 80 and over ; Community-Acquired Infections/complications/mortality/therapy ; Female ; Hospital Mortality ; Humans ; Hypercapnia ; Male ; Middle Aged ; Pneumonia, Bacterial/complications/*diagnosis/*mortality/therapy ; Predictive Value of Tests ; Prognosis ; Respiration, Artificial ; Respiratory Insufficiency/*diagnosis/etiology/*mortality/therapy ; Retrospective Studies ; Treatment Outcome

BACKGROUNDAlthough severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years.

METHODSForty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) < 10 served as group A and 21 with GCS = 10 as group B.

RESULTSCompared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P < 0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P < 0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P < 0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P < 0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P < 0.05 or P < 0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric content aspiration (1).

CONCLUSIONSSelected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD; a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.

Aged ; Brain Diseases ; therapy ; Carbon Dioxide ; blood ; Case-Control Studies ; Female ; Glasgow Coma Scale ; Humans ; Hypercapnia ; therapy ; Male ; Middle Aged ; Oxygen ; blood ; Positive-Pressure Respiration ; adverse effects ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; complications

BACKGROUND: There are contradictory reports concerning hypercapnia as a predictor of a better outcome in COPD. This study examined the clinical implications of hypercapnea in COPD patients (M:F = 59:19) who required mechanical ventilation. METHODS: The clinical parameters at the time of MICU admission, the total ventilation time, the APACHE II score and the pulmonary function testing were retrospectively analyzed between the survivors and nonsurvivors. RESULTS: Univariate analysis showed that compared with the nonsurvivors, the survivors had lower AaDO2 values (59.8+/-53.5 vs. 105.0+/-73.3 mmHg, p=0.000), higher PaCO2 values (64.9+/-16.0 vs. 48.9+/-17.8 mmHg, p=0.000), lower APACHE II scores (19.0+/-3.8 vs. 24.1+/-5.1, p=0.002), the more frequent application of initial noninvasive positive pressure ventilation (44.0 vs. 14.3%, p=0.008), and a lower combined rate of septic shock (4.0 vs. 39.3%, p=0.000). Multivariate analysis revealed that a lower PaCO2 (OR: 0.94, p=0.008), the presence of septic shock (OR: 10.16, p=0.011), a higher APACHE II score (OR: 1.22, p=0.040) and a longer ventilation time (OR: 1.002, p=0.041) were the risk factors for mortality. A lower PaCO2 was also verified as the predictor for mortality by multivariate analysis when excluding septic shock. CONCLUSIONS: Hypercapnia at admission is thought to be an independent predictor of better survival for the COPD patients who require mechanical ventilation.
*Treatment Outcome ; Survival Analysis ; Risk Factors ; Retrospective Studies ; Respiratory Insufficiency ; *Respiration, Artificial/methods ; Pulmonary Disease, Chronic Obstructive/*mortality/therapy ; Prognosis ; Patient Admission ; Multivariate Analysis ; Male ; *Hypercapnia ; Humans ; Female ; Biological Markers ; Aged ; APACHE

OBJECTIVETo explore the effects of safflower injection on prevention and treatment of hypoxic pulmonary hypertension and clarify the function of the endoplasmic reticulum stress apoptosis pathway during the process.

METHODSThirty male SD rats were randomly grouped as normal control group, hypoxia-hypercapnia group and hypoxia+safflower group. The latter two groups were put in the cabin with oxygen concentration ranged from 9% to 11% and carbon dioxide concentration from 5% to 6%. The pulmonary artery pressure and the index of right ventricular hypertrophy were determined after hypoxia exposure (8 h/dx28 d). Changes in morphology of lung tissue were observed by electron microscopy. To explore the possible mechanisms, we also detected apoptosis and apoptosis-related genes/proteins in lung tissue by TUNEL reactivity and PCR and Western blot.

RESULTSCompared with the normal control group, pulmonary artery pressure and the index of right ventricular hypertrophy in hypoxia group were 45% and 33.4% higher, respectively. Tiny blood vessel wall of lungs was thickened and edema, and proliferation of collagen fibers was obvious under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed more high brightness green fluorescence (+-++), but less green fluorescence showed in the pulmonary vascular smooth muscle cell layer, and apoptosis index (AI) value was 150% higher; gene and protein expression levels of endoplasmic reticulum stress pathway were increased. Compared with hypoxia-hypercapnia group, pulmonary artery pressure and the index of right ventricular hypertrophy in the hypoxia+safflower group were 18% and 15.6% lower, respectively; collagen fibers were decreased, and smooth muscle cells and epithelial cells were got apoptotic-like changes under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed brighter green fluorescence (++-+++); the high brightness green fluorescence showed in pulmonary vascular smooth muscle cell layer, and apoptotic index (Al) value was 40% higher; gene and protein expressions of endoplasmic reticulum stress pathway were significantly upregulated.

CONCLUSIONOur findings demonstrate that safflower injection could activate endoplasmic reticulum stress-induced apoptosis and especially promote apoptosis in pulmonary vascular smooth muscle cells.

Animals ; Apoptosis ; drug effects ; Carthamus tinctorius ; chemistry ; Endoplasmic Reticulum Stress ; drug effects ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Hypoxia ; physiopathology ; Lung ; cytology ; physiopathology ; Male ; Myocytes, Smooth Muscle ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the mechanism of how curcumin improves pulmonary vascular remodeling associated with chronic pulmonary arterial hypertension.

METHODSThe model of chromic hypoxia hypercapniapulmoary remodeling was made. Twenty-four male rats were randomly divided into 4 groups (n = 6): group I (normoxia control group), group II (hypxia and hypercapnia model group), group II (disodium cromoglycate control group), group IV (curcumin treated group). The last 3 group rats were put in a hypoxia cabin where the concentrate of O2 was 8% - 11% and the concentrate of CO2 was 3% - 5%, for 8 h a day and lasting 4 w in total. Group III rats were intraperitoneally injected with disodium cromoglycate (20 mg/kg) and group IV rats were administrated with curcumin by gavage (150 mg/kg). The morphological changes of pulmonary vessel walls and the ultrastructure of mast cells were observed by the optics microscope and the transmission electron microscope. Mast cells and its degranulation state were measured by toluidine blue staining and immunohistochemistry. Data were expressed as means ± SD (standard deviation) and analyzed with SPSS17.0 software.

RESULTS(1) By optics microscopy observation, the value of WA/TA was significantly higher in II group than other groups (P < 0.05). (2) Electron microscope showed that the endothelial cells of pulmonary arterioles in III and IV group were near to I group and the proliferation of pulmonary arterial media smooth cell layer and collagen fibers in adventitia was much lighter than those in II group. The membrane of mast cells was more intact in I, III, IV group than II group. (3) The number of mast cells, the degranulation rate of master cells and the number of positive tryptase stained cells in II group were significantly more than those in other groups. (P < 0.05).

CONCLUSIONCurcumin may inhibit the remodeling of pulmonary vessel induced by chronic hypoxia hypercapnia by mast cell regulation.

Animals ; Cell Degranulation ; Curcumin ; pharmacology ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; Hypoxia ; physiopathology ; Lung ; pathology ; Male ; Mast Cells ; physiology ; ultrastructure ; Pulmonary Artery ; drug effects ; Rats ; Rats, Sprague-Dawley ; Vascular Remodeling ; drug effects

BACKGROUNDPulmonary arterial hypertension (PAH) is characterized by suppressing apoptosis and enhancing cell proliferation in the vascular wall. Inducing pulmonary artery smooth muscle cells (PASMC) apoptosis had been regarded as a therapeutic approach for PAH. Oridonin can cause apoptosis in many cell lines, while little has been done to evaluate its effect on PASMC.

METHODSThirty male Sprague-Dawley rats were randomly assigned to three groups: normal control (NC); hypoxia-hypercapnia (HH); Hypoxia-hypercapnia + oridonin (HHO). Rats were exposed to hypoxia-hypercapnia for four weeks. Cultured human PASMC (HPASMC) were assigned to three groups: normoxia (NO); hypoxia (HY); hypoxia + oridonin (HO). The mean pulmonary artery pressure, mass ratio of right ventricle over left ventricle plus septum (RV/(LV + S)), the ratio of thickness of the pulmonary arteriole wall to vascular external diameter (WT%) and the ratio of the vessel wall area to the total area (WA%) were measured. Morphologic changes of pulmonary arteries were observed under light and electron microscopes. The apoptotic characteristics in vitro and in vivo were detected.

RESULTSThe mPAP, RV/(LV + S), WT%, and WA% in the HH group were significantly greater than those in the NC (P < 0.01) and HHO groups (P < 0.01); the activities of caspase-3 and caspase-9, and the expressions of Bax, cyt-C and apoptotic index (AI) in the group HH were less than those in the NC and HHO groups; and the expression of Bcl-2 in group HH was greater than that in the NC and HHO groups. HPASMC mitochondrial membrane potentials in group HO was lower than in group HY (P < 0.01), and cyt-C in the cytoplasm, AI, and caspase-9 in the HO group were greater than that in the HY group (P < 0.01), but the expression of Bcl-2 in the HO group was less than that in the HY group (P < 0.05).

CONCLUSIONSThe results suggest that oridonin can lower pulmonary artery pressure effectively, and inhibit pulmonary artery structural remodeling by inducing smooth cell apoptosis via a mitochondria-dependent pathway.

Animals ; Antihypertensive Agents ; pharmacology ; Apoptosis ; Blotting, Western ; Diterpenes, Kaurane ; pharmacology ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; Hypoxia ; physiopathology ; Immunohistochemistry ; Male ; Membrane Potential, Mitochondrial ; Microscopy ; Microscopy, Electron, Transmission ; Pulmonary Artery ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate clinical characteristics and PHOX2B gene mutations in congenital central hypoventilation syndrome (CCHS) and to facilitate the early diagnosis and management of CCHS and reduce the misdiagnosis.

METHODClinical data of 3 infants with CCHS who had recurrent respiratory failure episodes and dependent on mechanical ventilation support in 3 from March 2008 to April 2012 were analyzed, and blood gas analysis was performed respectively in the awaken and sleeping status. Gene sequencing was used for detection of PHOX2B gene mutation.

RESULTAll the three patients had adequate ventilation during awaken time, but they presented with abnormal frequency and shallow breathing associated with alveolar hypoventilation after falling asleep. Blood gas analysis showed hypercapnia and CO2 partial pressure was consistently over 60 mm Hg (1 mm Hg = 0.133 kPa) after falling asleep, which is in accordance with the clinical features of CCHS. The PHOX2B gene sequencing showed that 6 GCN repeats were inserted at exon3 of PHOX2B in case 1, at same position, 5 GCN repeats were inserted in case 2 and 3.

CONCLUSIONNormal ventilation in awaken status while shallow slow breathing accompanied with hypercapnia in sleep are the main clinical characteristics of CCHS, which requires mechanical ventilation. Acquired mutation in exon 3 of PHOX2B gene encoding repeated GCN sequence seems to be the molecular etiology of these three patients.

Alanine ; genetics ; Blood Gas Analysis ; Carbon Dioxide ; blood ; DNA Mutational Analysis ; Exons ; Female ; Homeodomain Proteins ; genetics ; Humans ; Hypercapnia ; diagnosis ; etiology ; Hypoventilation ; congenital ; diagnosis ; genetics ; therapy ; Infant ; Infant, Newborn ; Male ; Mutation ; Oxygen Inhalation Therapy ; Polymerase Chain Reaction ; Polysomnography ; Respiration, Artificial ; Retrospective Studies ; Sleep Apnea, Central ; diagnosis ; genetics ; therapy ; Transcription Factors ; genetics