慢性阻塞性肺疾病患者膈肌功能与CAT评分相关研究

目的探讨慢性阻塞性肺疾病(简称慢阻肺)患者平板数字化X线摄影检测膈肌功能与慢阻肺评估量表得分之间关系,为患者肺功能评估提供参考。方法 2013年3月31日至2014年5月31日共56例慢阻肺患者,行平板数字化X线摄影系统检查和CAT评分,统计结果采用均数±标准差,数据组间分析采用pearson相关分析。结果患者平板数字化X线摄影系统膈肌移动度、膈肌弧度与CAT评分之间为负相关,结果有统计学意义。结论平板数字化X线摄影系统与慢阻肺评估量表具有一致性,结合双方优势有利于更好进行肺功能评估。     

Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD.

STUDY OBJECTIVES: To investigate the possible relationship between functional respiratory impairment measured by FEV1 and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD. DESIGN: Multicenter, cross-sectional, epidemiologic study. SETTING: Pneumology units in six secondary or tertiary hospitals in Spain. PATIENTS: Ninety-one patients with acute exacerbation of COPD were included. INTERVENTIONS: A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10(6) cfu (> 10(5) for Streptococcus pneumoniae) in samples with < 10 epithelial cells and > 25 leukocytes per low magnification field (x 100). RESULTS: Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S. pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P. aeruginosa and H. influenzae were isolated more frequently among the patients with FEV1 < 50% than among those with FEV1 > 50% (p < 0.05). All patients with P. aeruginosa in sputum had FEV1 < 1,700 mL. FEV1 < 50% was associated with a very high risk of P. aeruginosa or H. influenzae isolation: the odds ratios (ORs) are 6.62 (95% confidence interval [CI], 1.2 to 123.6) and 6.85 (95% CI, 1.6 to 52.6), respectively. Furthermore, active tobacco smoking was associated with a high risk of H. influenzae isolation (OR, 8.1; 95% CI, 1.9 to 43.0). CONCLUSIONS: Patients with the greatest degree of functional impairment, as measured by their FEV1, presented a higher probability of having an isolation of P. aeruginosa or H. influenzae in significant concentrations in sputum during an exacerbation. The diagnostic yield of sputum in patients with an FEV1 > 50% was low, with a predominance of non-PPMs. Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.     

Increased glutathione disulfide and nitrosothiols in sputum supernatant of patients with stable COPD

STUDY OBJECTIVES: Increased oxidant burden is involved in the pathogenesis of COPD. Glutathione (GSH) is a major antioxidant scavenging reactive oxygen and nitrogen species. We studied the concentrations of total and reduced GSH, glutathione disulfide (GSSG), and nitrosothiols in sputum supernatant of patients with COPD. DESIGN: Twenty-five patients with moderate-to-severe COPD (FEV(1) 61 +/- 12% of predicted) and 25 healthy nonsmoking control subjects underwent sputum induction. Sputum total GSH and GSSG were measured spectrophotometrically, and nitrosothiols were quantified by enzyme assay. Exhaled nitric oxide (eNO) was also measured to correlate eNO with nitrosothiols in induced sputum. MEASUREMENTS AND RESULTS: Compared with healthy subjects, patients with COPD had increased sputum neutrophils (geometric mean, 65%; 95% confidence interval [CI], 57.5 to 71; vs 21%; 95% CI, 13.2 to 31.6; p < 0.001); total GSH (geometric mean, 7.1 micromol/L; 95% CI, 2.95 to 17; vs 5.1 micromol/L; 95% CI, 3.2 to 8.1; p = 0.024); GSSG (geometric mean, 4.1 micromol/L; 95% CI, 1.7 to 10; vs 0.84 micromol/L; 95% CI, 0.35 to 1.99; p = 0.002); and nitrosothiols (geometric mean, 60.4 micromol/L; 95% CI, 40 to 95.5; vs 38 micromol/L; 95% CI, 31.6 to 43.6; p = 0.04). Sputum GSSG was positively correlated with neutrophils (rho = 0.47, p = 0.016) and nitrosothiols (rho = 0.49, p = 0.024) in patients with COPD, whereas there was no correlation of eNO with nitrosothiols (rho = 0.38, p = 0.1). CONCLUSIONS: Sputum concentrations of GSSG and nitrosothiols are increased in patients with COPD and associated with neutrophilic inflammation. These data underline the role of oxidative stress in the pathogenesis of COPD, and suggest that GSH is important to scavenge both reactive oxygen and nitrogen species.     

Glutathione and nitrite levels in induced sputum at COPD patients and healthy smokers

Objectives

The role of oxidative stress at the pathogenesis of chronic obstructive pulmonary disease (COPD) is known. The aim of this study is to investigate the oxidative stress with sputum induction that is a simple method in COPD patients and healthy smokers.

Methods

Sputum induction was performed in 21 COPD patients (10 stable, 11 acute exacerbations), nine healthy smokers, and ten healthy non-smokers. Glutathione, NO₂^– levels, and cell counts at sputum, and plasma NO₂^– contents were evaluated in all subjects.

Results

Mean sputum glutathione and NO₂^– levels were significantly higher in acute exacerbations with COPD patients than healthy smokers (P=0.007 and P<0.001 respectively), and non-smokers (P<0.001 and P<0.001 respectively). On the other hand, sputum glutathione and NO₂^– levels did not show significant differences between stable and acute exacerbations with COPD patients. Although, sputum glutathione levels were higher in stable COPD patients than healthy smokers’, no statistically significant difference was established. In addition, sputum glutathione levels were significantly higher in healthy smokers than non-smokers (P<0.001).

Conclusions

As a result, we can say that oxidative stress increases not only in COPD patients but also in healthy smokers. In addition, sputum induction that is a simple method can be used to demonstrate to show oxidative stress.     

3-Chlorotyrosine in sputum of COPD patients: relationship with airway inflammation

The airways of patients with chronic obstructive pulmonary disease (COPD) are associated with increased numbers of inflammatory cells, in particular neutrophils and macrophages. Contained within the primary granules of neutrophils is the heme enzyme called myeloperoxidase (MPO) that has been used as a biomarker of neutrophilic inflammation in COPD and other inflammatory diseases. MPO is the only enzyme in the body that produces hypochlorous acid (HOCl), which effectively chlorinates tyrosine residues in proteins. The presence of 3-chlorotyrosine (3Cl-Tyr) in sputum of COPD patients has yet to be established. Spontaneously produced sputum was collected from 14 stable COPD patients, and ultra-centrifuged to prepare sol phase samples for analysis. Sputum 3Cl-Tyr levels were measured using Mass Spectrometry (LC-MSMS). Sputum MPO activity was measured using a standard chromogenic substrate assay. The Spearman rank correlation was used to analyse the data. We report for the first time the measurement of 3Cl-Tyr in sputum from stable COPD patients. The sputum levels of 3Cl-Tyr correlated well with sputum MPO activity (r = 0.88; p < 0.0001). The presence of 3Cl-Tyr in the sputum of stable COPD patients suggests an active process related to MPO that may play a role in the pathophysiology of this disease.     

CXCR3 and CCR5 chemokines in induced sputum from patients with COPD

BACKGROUND: COPD is associated with increased numbers of CD4(+) and CD8(+) lymphocytes and macrophages in the small airways and lung parenchyma. The chemokines regulating T-cell recruitment into the lung are unknown but may involve CXCR3 and CCR5 chemoattractants. The aims of this study were to determine the concentrations of CXCR3 chemokines CXCL9, CXCL10, CXCL11, and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers, and nonsmokers, and to examine the relationship between chemokine expression, inflammatory cells, and airway obstruction. METHODS: Differential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were measured in induced sputum from nonsmokers (n = 18), smokers (n = 20), and COPD patients (n = 35) using an enzyme-linked immunosorbent assay. RESULTS: Concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were significantly increased in the sputum of patients with COPD when compared with nonsmokers but not smokers without obstruction: CXCL9 (median, 14.3 pg/mL; interquartile range [IQR], 6.5 to 99.3; vs median, 1.4 pg/mL; IQR, 0 to 10.4 [p < 0.001]; vs 8.5 pg/mL; IQR, 0 to 16.0, respectively); CXCL10 (16.9 pg/mL; IQR, 6.2 to 148.8; vs 3.7 pg/mL; IQR, 0 to 18.8 [p < 0.05]; vs 11.3 pg/mL; IQR, 3.7 to 46.7); CXCL11 (58.1 pg/mL; IQR, 34.5 to 85.3; vs 33.5 pg/mL; IQR, 23.2 to 49.7 [p < 0.05]; vs 49.8 pg/mL; IQR, 32.6 to 105.6); and CCL5 (59.9 pg/mL; IQR, 57.1 to 67.8; vs 33.5 pg/mL; IQR, 31.6 to 36.9 [p < 0.001]). CCL5 in sputum from smokers was also significantly increased compared with that from nonsmokers (median, 63.0 pg/mL; IQR, 60.8 to70.2; p < 0.001). There was a negative correlation between FEV(1) percentage of predicted, FEV(1)/FVC ratio, and percentage of macrophages, and all the chemokines analyzed. Neutrophil numbers correlated positively with the concentrations of chemokines. CONCLUSIONS: CXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with nonsmokers, and may be important in COPD pathogenesis.     

Benefit of amoxicillin in differentiating between TB suspects whose initial AFB sputum smears are negative.

SETTING: Out-patient dispensary in Conakry, Guinea, West Africa. OBJECTIVE: To differentiate between pulmonary tuberculosis (PTB) and non-PTB diseases among 204 acid-fast bacilli (AFB) smear-negative adult TB suspects. DESIGN: We derived scores from clinical, serological and radiological findings among PTB suspects aged > or = 15 years who, after having had three AFB-negative smears, were treated for 10 days with amoxicillin (AMX, 1.5 g/day). RESULTS: At the selected cut-off score from model 1 (clinical), sensitivity for PTB was 95%, specificity 40%, negative predictive value (NPV) 84%, and positive predictive value (PPV) 69%. Comparable values from model 2 (clinical + serological + radiological) were: sensitivity 99%, specificity 45%, NPV 97%, and PPV 71%. Results from AMX were better: sensitivity 92%, specificity 93%, NPV 94%, and PPV 91%. Of the 117 suspects who failed to respond clinically and radiographically to AMX and remained AFB smear-negative, 110 (94%) had PTB, confirmed either by positive culture (73 patients) or response to anti-tuberculosis treatment (37 patients). CONCLUSION: The clinical and radiographic response to AMX is better than derived scores at differentiating between PTB and non-PTB in TB suspects presenting to a dispensary in Guinea, a low HIV-seroprevalence country.     

Cough and sputum production as risk factors for poor outcomes in patients with COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in developed countries, and its prevalence is projected to increase over the coming decades. According to the World Health Organization, COPD will become the third leading cause of death worldwide by 2020. COPD has a chronic and progressive course, and is often aggravated by exacerbations, which typically arise as a result of bronchial infection. Exacerbations are characterised by periods of increasing acute symptoms, particularly cough, dyspnoea and production of sputum, which worsen airflow obstruction, further impair quality of life and generally require a change in regular medication. Exacerbations are the most common cause of medical visits, hospital admissions and death in patients with COPD, and frequent exacerbations worsen health status and may cause a permanent decline in lung function. Chronic cough and sputum production are common in the general population, but significantly more prevalent in patients with respiratory disorders; these symptoms have been suggested as a risk factor for exacerbations of COPD. This article will review the consequences of chronic cough and sputum production in patients with COPD and analyse whether these risk factors may be useful for identifying a specific phenotype of patient that requires different management to reduce the occurrence of exacerbations.     

Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia

PURPOSE: Patients with pneumonia often remain hospitalized after becoming clinically stable, without demonstrated benefits on outcome. The purposes of this study were to assess the relation between length of hospital stay and daily medical care costs and to estimate the potential cost savings associated with a reduced length of stay for patients with pneumonia. SUBJECTS AND METHODS: As part of a prospective study of adults hospitalized with community-acquired pneumonia at a community hospital and two university teaching hospitals, daily medical care costs were estimated by multiplying individual charges by department-specific cost-to-charge ratios obtained from each hospital's Medicare cost reports. RESULTS: The median total cost of hospitalization for all 982 inpatients was $5, 942, with a median daily cost of $836, including $491 (59%) for room and $345 (41%) for non-room costs. Average daily non-room costs were 282% greater on the first hospital day, 59% greater on the second day, and 19% greater on the third day than the average daily cost throughout the hospitalization (all P <0.05), and were 14% to 72% lower on the last 3 days of hospitalization. Average daily room costs remained relatively constant throughout the hospital stay, with the exception of the day of discharge. A projected mean savings of $680 was associated with a 1-day reduction in length of stay. CONCLUSIONS: Despite institutional differences in total costs, patterns of daily resource use throughout hospitalization were similar at all institutions. A 1-day reduction in length of stay might yield substantial cost-savings.     

Physical activity and hospitalization for exacerbation of COPD

BACKGROUND: Acute exacerbations (AEs) have a negative impact on various aspects of the progression of COPD, but objective and detailed data on the impact of hospitalizations for an AE on physical activity are not available.Objective and measurements: We aimed to investigate physical activity using an activity monitor (DynaPort; McRoberts; the Hague, the Netherlands), pulmonary function, muscle force, 6-min walking distance, and arterial blood gas levels in 17 patients (mean age, 69 +/- 9 years [+/- SD]; body mass index, 24 +/- 5 kg/m(2)) at the beginning and end of a hospitalization period for an AE and 1 month after discharge. RESULTS: Time spent on weight-bearing activities (walking and standing) was markedly low both at day 2 and day 7 of hospitalization (median, 7%; interquartile range [IQR], 3 to 18% of the time during the day; and median, 9%; IQR, 7 to 21%, respectively) and 1 month after discharge (median, 19% [IQR, 10 to 34%]; Friedman test, p = 0.13). Time spent on weight-bearing activities was positively correlated to quadriceps force at the end of the hospitalization period (r = 0.47; p = 0.048). Patients with hospitalization for an AE in the previous year had an even lower activity level when compared to those without a recent hospitalization. In addition, patients with a lower activity level at 1 month after discharge were more likely to be readmitted in the following year. CONCLUSIONS: Patients with COPD are markedly inactive during and after hospitalization for an AE. Efforts to enhance physical activity should be among the aims of the disease management during and following the AE periods.     

Perforin expression and cytotoxic activity of sputum CD8+ lymphocytes in patients with COPD

BACKGROUND: Previous studies have shown that the inflammatory response to cigarette smoking differs between smokers who acquire COPD and those who do not, and the CD8(+) T- lymphocytes have been identified as a key player in this response. OBJECTIVE: To investigate the cytotoxic activity and perforin expression of CD8(+) lymphocytes in the airway lumen of patients with COPD. METHODS: Thirty-six male smokers with COPD, 25 male smokers without COPD, and 10 healthy nonsmokers participated in the study. T-lymphocytes of induced sputum samples were labeled with appropriate monoclonal antibodies and measured using flow cytometry. The cytotoxic activity of CD8(+) cells was defined by incubating them with specific target cells (K562). RESULTS: The percentage and the total number of CD8(+) lymphocytes were significantly higher in COPD smokers compared to non-COPD smokers (p = 0.01 and p = 0.005, respectively) or to healthy nonsmokers (p = 0.02 and p = 0.01, respectively). Perforin expression in CD8(+) cells was significantly higher in smokers with COPD compared to the other two groups (p = 0.001). Increased cytotoxic activity of T cells was also observed in induced sputum of patients with COPD in comparison to the other two groups. CONCLUSION: CD8(+) cells are not only increased in number in sputum samples of smokers with COPD but are highly activated, expressing high levels of perforin. These findings suggest that CD8(+) T-lymphocytes play a significant role in the inflammatory process of COPD.