Objective To investigate the distribution and antibiotic resistance of pathogens isolated fromlower respiratory tract in mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease ( AECOPD) . Methods The patients with AECOPD, who were hospitalized in RICU from January 2008 to November 2009, were divided into a community infection group and a nosocomial infection group. Lower respiratory tract isolates were collected by bronchoscopic protected specimen brush for bacterial identification and susceptibility test. Results 134 cases were enrolled in the study, with 75 cases in thecommunity infection group and 59 cases in the nosocomial infection group. The positive detection rate in the nosocomial infection group was significantly higher than that in the community infection group [ 81. 4%( 48/59) vs. 54. 7% ( 41/75) ] . In the community infection group, 49 strains were isolated, in which gramnegativebacteria, gram-positive bacteria, and fungi accounted for 55. 1% , 28. 6% , and 16. 3% , respectively.In the nosocomial infection group, 55 strains were isolated, in which gram-negative bacteria, gram-positive bacteria, and fungi accounted for 61. 8% , 21. 8% , and 16. 4%, respectively. There was no significant difference in the microbial distribution between the two groups ( P gt; 0. 05) . The detection rate of ESBLs producing strains in the nosocomial infection group was significantly higher than that in the community infection group ( 58. 8% vs. 37% ) . The resistance rates in the nosocomial groups were higher than those in the community infection group. Conclusions Antibiotic resistance is serious in mechanically ventilated patients with AECOPD, especially in the nosocomial infection patients. The increased fungi infection and drug resistance warrant clinicians to pay more attention to rational use of antibiotics, and take effective control measures.
Objective To investigate whether ADAM33 ( A disintegrin and metalloproteinase 33) gene polymorphismhas effect on the airway inflammation of COPD. Methods A total of 312 COPD patients were recruited for this study. Four polymorphic loci ( T2, T1, S2, and Q-1) of ADAM33 were selected for genotyping by using the polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) method. Total and differential cell counts, contents of TNF-α, IL-6, IL-8, and VEGF in induced sputumwere detected. The relationship between genotypes and inflammatory reaction was analyzed. Results On locus T2, the cell counts and content of TNF-αin induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.01 and Plt;0.05) . On locus T1, the lymphocyte counts in induced sputumincreased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.05) ; but the content of IL-8 in induced sputumwas higher in AA and AG genotypes ( Plt;0.05) . On locus Q-1, the contents of VEGF and IL-8 in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes (Plt;0.05) . On locus S2, the total cell counts in induced sputumincreased significantly in the carriers with GG genotype than those with CC and CG genotypes ( Plt;0.05) , and the content of IL-8 in induced sputum increased significantly in GG genotype ( Plt;0.01 ) . Conclusion These results suggest that ADAM33 polymorphism may participate the pathogenesis of COPD by promoting airway inflammation.
Objective To evaluate and select essential medicine for chronic obstructive pulmonary diseases (COPD) using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Nine guidelines were included (eight foreign guidelines, one domestic guideline; seven based on evidence, two based on expert consensus). (2) A result of one domestic RCT (n=72, high quality) indicated that tiotropium could significantly improve pulmonary function of severe COPD patient complicated with respiratory failure and increase their quality of life (SGRQ score: MD=–10.8%, 95%CI –12.2% to –9.4%). A result of one RCT (n=156, moderate quality) with 3-month follow-up indicated that tiotropium could significantly improve the proportion of measured value to expected value of FEV1 in patients with mild and moderate COPD in stationary phase (MD=10.3%, 95%CI 8.1% to 12.5%). A result of two RCTs (n=160, low quality) indicated that compound ipratropium bromide had efficiencies of 84.2% to 87.5% for moderate and severe COPD. A result of one RCT (n=60, moderate quality) indicated that salmeterol/fluticasone (inhalation) was superior to placebo for improving mild and moderate COPD in stationary phase. A result of one RCT (n=725, moderate quality) indicated that tiotropium combined with salmeterol/fluticasone for COPD in stationary phase was superior to tiotropium alone. A result of one RCT (n=110, low quality) indicated that nebulized budesonide inhalation had an efficiency of 86.8% for acute exacerbation of COPD (AECOPD) and an incidence of 7.9% as to adverse reaction that mainly included laryngo-pharyngeal irritation. (3) Imipenem, meropenem, cefoperazone/ sulbactam and ceftazidime were effective for COPD with low drug resistance rates in treating COPD caused by non-ICU pathogens (less than 8%). Conclusion (1) We offer a b recommendation for tiotropium, ipratropium, salbutamol, formoterol, salmeterol and theophylline used in the treatment of COPD in stationary and exacerbation phases, a b recommendation for streptococcus pneumoniae and influenza vaccines in preventing the deterioration of COPD, a b recommendation for inhaled corticosteroids (ICS) used in the treatment of COPD in stationary phase and a b recommendation for corticosteroids (for oral use) for AECOPD. (2) We offer a b recommendation for cefoperazone/sulbactam, imipenem and meropenem used in the treatment of moderate and severe AECOPD. (3) We offer a weak recommendation for ceftazidime, ciprofloxacin, lavofloxacin, moxifloxacin, amoxicillin amp; clavulanate potassium, amoxicillin, azithromycin, clarithromycin and doxycycline as first-line and second-line antibiotics for mild and moderate AECOPD, and a weak recommendation for compound sulfamethoxazole, cefatriaxone, cefotaxime and cefuroxime used in the treatment of severe and extremely severe COPD, mucolytic agents used in the treatment of stable COPD with difficult expectoration. (4) We make a recommendation against antibiotics, expectorants and corticosteroids (for oral use) as routine use in stationary phase of COPD.
Objective To investigate the role of AKT/FOXOs /atrogin-1/MuRF1 signaling pathway in skeletal muscle atrophy in rats with chronic obstructive pulmonary diseases( COPD) .Methods Passive cigarette smoking was used to establish COPD model. The protein expression of atrogin-1, MuRF1, FOXO-1, phosohorylated-AKT and total AKT were measured by Western blot. The mRNA expression of atrogin-1, MuRF1 and FOXO-1 were measured by reverse transcription-polymerase chain reaction( RT-PCR) . Results Compared with the control group, the mRNA expressions of atrogin-1, MuRF1 and FOXO-1 significantly increased in extensor digitorum longus ( EDL) of the COPD group (Plt;0.05 ) . Meanwhile the protein expression of atrogin-1 and MuRF1 significantly increased in the COPD group(Plt;0.05) , while the protein expression of FOXO-1 was not significantly different between two groups(Pgt;0.05) . In addition, , the protein expression of phosohorylated-AKTand the ratio of phosohorylated-AKT to total AKT significantly increased in EDL of the COPD group(Plt;0.05) . Conclusion The mRNA and protein expression of AKT/FOXOs/ atrogin-1 /MuRF1 in skeletal muscle are significantly increased in COPD rats, suggesting that AKT/FOXOs/ atrogin-1 /MuRF1 signalling pathway plays a crucial role in skeletal muscle atrophy of COPD.
自从2001 年颁布第1 版慢性阻塞性肺疾病 ( COPD) 诊断、处理和预防全球策略以来，已经整整10 年了，10 年中COPD 的研究取得了相当大的进展。2011 年底颁布的“Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease ( Revised 2011) ”( 简称全球策略修订版) 在原版本的基础上, 根据 COPD 临床研究的最新进展进行了重大修改。
ObjectiveTo investigate the role of PI3K/AKT/mTOR signaling pathway in skeletal muscle atrophy in rats with chronic obstructive pulmonary diseases(COPD). MethodsPassive cigarette smoking was used to establish COPD model.The protein expression of PI3K, total mTOR, phosphorylated-mTOR, total GSK-3β, phosphorylated-GSK-3β, total 4E-BP1, phosphorylated-4E-BP1, total p70S6K1 and phosphorylated-p70S6K1 in extensor digitorum longus of rats were measured by Western blot. ResultsThe protein expression of PI3K was not significantly different between two groups(P > 0.05).Compared with the control group, the protein expression of total mTOR, phosphorylated-mTOR, total GSK-3β, and phosphorylated-GSK-3βincreased significantly in the COPD group(P < 0.05).The protein expression of total 4E-BP1 and total p70S6K1 were not significantly different between two groups(P > 0.05).While the protein expression of phosphorylated-4E-BP1 and phosphorylated-p70S6K1 significantly increased in the COPD group(P < 0.05). ConclusionThe protein expressions of PI3K/AKT/mTOR signaling pathway in extensor digitorum longus increased significantly in COPD rats, suggesting that the activity of PI3K/AKT/mTOR signaling pathway increased, which may be one of the compensatory mechanism of skeletal muscle atrophy in COPD.
ObjectiveTo compare the therapeutic effects of invasive-high-flow oxygen therapy (HFNC) and invasive-non-invasive ventilation (NIV) sequential strategies on severe respiratory failure caused by chronic obstructive pulmonary disease (COPD), and explore the feasibility of HFNC after extubation from invasive ventilation for COPD patients with severe respiratory failure.MethodsFrom October 2017 to October 2019, COPD patients with type Ⅱ respiratory failure who received invasive ventilation were randomly assigned to a HFNC group and a NIV group at 1: 1 in intensive care unit (ICU), when pulmonary infection control window appeared after treatments. The patients in the HFNC group received HFNC, while the patients in the NIV group received NIV after extubation. The primary endpoint was treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 hour, 24 hours, and 48 hours after extubation, total respiratory support time after extubation, daily airway care interventions, comfort scores, and incidence of nasal and facial skin lesions, ICU length of stay, total length of stay and 28-day mortality after extubation.ResultsOne hundred and twelve patients were randomly assigned to the HFNC group and the NIV group. After secondary exclusion, 53 patients and 52 patients in the HFNC group and the NIV group were included in the analysis respectively. The treatment failure rate in the HFNC group was 22.6%, which was lower than the 28.8% in the NIV group. The risk difference of the failure rate between the two groups was –6.2% (95%CI –22.47 - 10.43, P=0.509), which was significantly lower than the non-inferior effect of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of –38.4% (95%CI –62.5 - –3.6, P=0.043). One hour after extubation, the respiratory rate of both groups increased higher than the baseline level before extubation (P<0.05). 24 hours after extubation, the respiratory rate in the HFNC group decreased to the baseline level, but the respiratory rate in the NIV group was still higher than the baseline level, and the respiratory rate in the HFNC group was lower than that in the NIV group [(19.1±3.8) vs. (21.7±4.5) times per minute, P<0.05]. 48 hours after extubation, the respiratory rates in the two groups were not significantly different from their baseline levels. The average daily airway care intervention in the NIV group was 9 (5 - 12) times, which was significantly higher than the 5 (4 - 7) times in the HFNC group (P=0.006). The comfort score of the HFNC group was significantly higher than that of the NIV group (8.6±3.2 vs. 5.7±2.8, P= 0.022), while the incidence of nasal and facial skin lesions in the HFNC group was significantly lower than that in the NIV group (0 vs. 9.6%, P=0.027). There was no significant difference in dyspnea score, length of stay and 28-day mortality between the two groups.ConclusionsThe efficacy of invasive-HFNC sequential treatment on COPD with severe respiratory failure is not inferior to that of invasive-NIV sequential strategy. The two groups have similar treatment failure rates, and HFNC has better comfort and treatment tolerance.
Objective To systematically evaluate the risk factors for secondary respiratory failure (RF) on chronic obstructive pulmonary disease (COPD), so as to provide evidence for formulating prevention and control strategies. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP databases and SinoMed were searched for articles published from the dates of establishment of databases to August 2021. To collect the relevant case-control studies or cohort studies on the risk factors of secondary RF in patients with COPD. The patients were divided into two groups, RF group and non RF group. Meta-analysis was carried out with RevMan 5.3 software after selecting literature, extracting data and evaluating quality according to inclusion and exclusion criteria. Results A total of 16 case-control studies involving 2 417 patients were included. There were 856 cases in RF group and 1 561 cases in non RF group. The results of meta-analysis showed that age [mean difference (MD)=0.58 years, 95% confidence interval (CI) (0.18, 0.97) years, P=0.004], number of acute attacks per year [MD=2.68 times, 95%CI (2.58, 2.78) times, P<0.001], number of acute attacks per year over 3 [odds ratio (OR)=3.37, 95%CI (2.40, 4.73), P<0.001], serum albumin level [MD=−2.93 g/L, 95%CI (−3.92, −1.94), P<0.001], serum uric acid [MD= −59.91 mmol/L, 95%CI (−66.57, −53.25) mmol/L, P<0.001], nosocomial infection [OR=4.53, 95%CI (3.44, 5.98), P<0.001], no-inhaled glucocorticoid [OR=3.63, 95%CI (2.95, 4.48), P<0.001], acid-base imbalance [OR=13.22, 95%CI (10.14, 17.23), P<0.001], COPD very serious [OR=1.82, 95%CI (1.50, 2.21), P<0.001], cardiovascular disease [OR=2.73, 95%CI (1.99, 3.74), P<0.001], kidney disease [OR=3.62, 95%CI (2.67, 4.90), P<0.001] were risk factors for RF in COPD. Sensitivity analysis showed that the results of meta-analysis were stable. Conclusion According to the results of meta-analysis, the risk factors of secondary RF in COPD can be identified in time and preventive measures can be taken to effectively reduce the incidence of aspiration failure and improve the prognosis and outcome of patients.
Objective To evaluate the correlation between blood eosinophilia and clinical characteristics, readmission rate and mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, VIP, and CBM databases were searched until October 31, 2021. Two researchers independently screened the literature, extracted the data, and evaluated the bias risk of the included studies. Meta-analysis was conducted by Rev Man v.5.4. Results Finally, 76 observational studies met the inclusion criteria, including 15 English literatures and 61 Chinese literatures. There were 8240 patients (34.20%) in the eosinophilia group (EOS≥2%) and 15854 cases (65.8%) in the eosinophil normal group (EOS<2%). Results of meta-analysis: (1) Inflammatory Index: eosinophilia group had lower C-reactive protein [MD=–8.44, 95%CI (–10.59, –6.29), P<0.05], and lower neutrophil to lymphocyte ratio [MD=–2.47, 95%CI (–3.13, –1.81), P<0.05]. (2) Hospitalization: eosinophilia group had shorter hospital stay [MD=–2.23, 95%CI (–2.64, –1.81), P<0.05] and lower in-hospital mortality [OR=0.41, 95%CI (0.31, 0.53), P<0.05], lower mechanical ventilation rate [OR=0.59, 95%CI (0.47, 0.75), P<0.05], lower hormone use rate [OR=0.91, 95%CI (0.85, 0.96), P<0.05]. (3) Follow-up results: eosinophilia group had a lower rate of readmission at 1 year [OR=0.78, 95%CI (0.66, 0.92), P<0.05] and a lower rate of death at 1 year [OR=0.78, 95%CI (0.62, 0.97), P<0.05]. Conclusions AECOPD patients with eosinophilia group were characterized by lower inflammatory indicators, shorter hospital stay, shorter in-hospital mortality, lower mechanical ventilation rate, lower hormone use rate, lower rate of acute exacerbation readmission, lower mortality rate and lower rate of follow-up after 1 year. This kind of patients with mild disease, good treatment effect, low risk of acute exacerbation.