Two cases of chronic obstructive pulmonary disease with undetectable diffusing capacity for carbon monoxide

Pulmonary diffusing capacity for carbon monoxide (DL_CO) is a valuable pulmonary function test to evaluate the gas exchange capacity of the lungs. Generally, DL_CO values are significantly lower in patients with chronic obstructive pulmonary disease (COPD), particularly in those with a predominantly emphysema phenotype. However, it is extremely rare that DL_CO values cannot be obtained for reasons other than technical errors. Herein, we report two patients with COPD in whom DL_CO values were undetectable without prolonging the breath-holding time for the test. We discuss possible mechanisms for these peculiar findings.     

慢性阻塞性肺疾病患者炎症细胞因子与肺通气功能的相关研究

目的　探讨慢性阻塞性肺疾病 (COPD)患者肺通气功能改变与炎症因子变化之间的关系。方法　稳定期COPD和慢性支气管炎 (简称慢支 )患者各 8例 ,,另有 8名健康者作为对照 ,进行肺功能检查 ,并经支气管肺泡灌洗获取肺泡巨噬细胞进行培养 ,采用酶联免疫吸附 (ELISA)方法测定大肠杆菌内毒素 (LPS)刺激后上清液中白细胞介素 8(IL 8)、IL 1β、IL 6和肿瘤坏死因子α(TNF α)的浓度 ,细胞因子之间相关性采用Pearson相关阵分析 ,肺功能值与细胞因子相关性采用多元后退回归法分析。结果　 (1)肺泡巨噬细胞释放IL 8:加入LPS后COPD组为 [(43± 2 7) μg/L和 (5 7± 41) μg/L],与正常对照组 [(13± 10 ) μg/L和 (2 0± 13 ) μg/L) ]比较差异有显著性 (P <0 .0 5 ) ;与慢支组 [(2 9± 2 1)μg/L和 (3 2± 2 3 ) μg/L]比较差异有显著性 (P >0 .0 5 )。 (2 )加入LPS前、后 ,COPD组、慢支组和正常对照组肺泡巨噬细胞释放IL 1β分别为 [(5 0± 41)ng/L、(94± 5 9)ng/L、(3 7± 3 2 )ng/L、(2 2 5± 10 8)ng/L、(15 3± 175 )ng/L、(70± 3 7)ng/L],与IL 8的释放呈正相关 (P <0 .0 5 ) ;三组肺泡巨噬细胞在LPS刺激后释放TNF α分别为 [(12 3 8± 679)ng/L、(3 0 88± 2 879)ng/L、(13 3 2± 1846)ng/L],与IL 1β呈正相     

Diffusing capacity for nitric oxide and carbon monoxide in patients with diffuse parenchymal lung disease and pulmonary arterial hypertension

BACKGROUND: The passage of carbon monoxide (CO) through the alveolocapillary membrane and into the plasma and intraerythrocytic compartments determines the diffusing capacity of the lung for CO (DLCO) as defined by the Roughton and Forster equation. On the other hand, the single-breath diffusing capacity of the lung for nitric oxide (DLNO) is thought to represent the true membrane diffusing capacity because of its very high affinity for hemoglobin (Hb) and its independence from pulmonary capillary blood volume. Therefore, the DLNO/DLCO ratio can be used to differentiate between thickened alveolocapillary membranes (both DLNO and DLCO are decreased, and the DLNO/DLCO ratio is normal) and decreased perfusion of ventilated alveoli (the DLNO less decreased than the DLCO; therefore, the DLNO/DLCO ratio is high) in patients with pulmonary disease. STUDY DESIGN: We measured the combined values of DLCO and DLNO in 41 patients with diffuse parenchymal lung disease (DPLD), 26 patients with pulmonary arterial hypertension (PAH), and 71 healthy subjects. RESULTS: The DLCO (corrected to the standard Hb value) was lowered in the DPLD group (64% of predicted) and in the PAH group (64% of predicted), and was normal in the control group (105% of predicted). The DLNO/DLCO ratio in patients with PAH (4.98) was significantly higher than that in patients with DPLD (4.56) and in healthy subjects (4.36). CONCLUSION: The DLNO/DLCO ratio is significantly higher in patients with PAH than in healthy subjects, although this ratio cannot be applied as a screening test to discriminate between patients with DPLD and PAH as the overlap between these groups is too large.     

Diffusing capacity for carbon monoxide in children with type 1 diabetes

Aims/hypothesis Few data are available on lung dysfunction in children with diabetes. We studied the association of pulmonary function variables (flows, volumes and alveolar capillary diffusion) with disease-related variables in children with type 1 diabetes mellitus.Methods We studied 39 children with type 1 diabetes (mean age 10.9±2.6 years, disease duration 3.6±2.4 years, insulin·kg^–1·day^–1 0.77±0.31) and 30 healthy control children (mean age 10.4±3.0 years). Pulmonary function tests included spirometry, N₂ wash-out and the single-breath diffusing capacity for carbon monoxide (DL_CO) corrected for the alveolar volume (DL_CO/V_A). Glycaemic control was assessed on the basis of HbA₁c, with HbA₁c values of 8% or less considered to indicate good glycaemic control, and HbA₁c values of 8% or more considered to indicate poor control.Results Children with poor glycaemic control had comparable percentage values for predicted flows and volumes but lower DL_CO/V_A values than children with good glycaemic control and healthy control children (86.7±12.6 vs 99.8±18.4 and 102.0±15.7; p<0.05). The predicted DL_CO/V_A percentages correlated with HbA₁c levels (r=–0.39, p=0.013). A multiple regression analysis (stepwise model) controlling for HbA₁c levels and other disease-related variables (age of disease onset, disease duration, daily insulin dose/kg, sex) identified HbA₁c levels as the sole predictor of DL_CO/V_A in percent.Conclusions/interpretation In children with type 1 diabetes, the diffusing capacity diminishes early in childhood and is associated with poor metabolic control. Although low DL_CO/V_A levels in these children probably reflect pulmonary microangiopathy induced by type 1 diabetes, other factors presumably influencing CO diffusion capacity measurements (e.g. a left shift in HbA₁c resulting in high O₂ binding and low CO binding) could explain the apparent capillary and alveolar basal membrane dysfunction.     

Familial aspects of ventilatory control in patients with chronic obstructive pulmonary disease

To determine whether abnormal chemical drives to breathe in patients with chronic obstructive pulmonary disease (COPD) antedate the development of chronic CO2 retention, we measured ventilatory and P0.1 responses to hypercapnia and hypoxia in 14 such patients and 23 of their normal adult offspring. Hypoxic responses in the patients were positively correlated with the mean hypoxic responses of their offspring. Neither the hypercapnic responses nor the resting breathing patterns of the patients were related to those of their offspring. Hypoxic response was lower in offspring of hypercapnic patients than in offspring of normocapnic patients. Blunt hypoxic responses in patients with COPD are influenced by familial factors and may represent a premorbid "risk factor" in the development of CO2 retention in this disease. This does not appear to be true for hypercapnic response or breathing pattern.     

Effect of carbon monoxide on exercise performance in chronic obstructive pulmonary disease

We evaluated the effect of breathing 100 ppm of carbon monoxide versus compressed, purified air for 1 hour on exercise performance in 10 patients with chronic obstructive pulmonary disease in a double-blind, randomized, crossover study. The mean arterial carboxyhemoglobin was 1.48 per cent in the carbon monoxide control period and increased from 1.43 to 4.08 per cent after breathing carbon monoxide (P less than 0.001). The mean arterial carboxyhemoglobin level was 1.52 percent in the air control period and decreased from 1.47 to 1.34 per cent after purified air (P less than 0.001). The mean exercise time until marked dyspnea decreased from 218.5 seconds in the carbon monoxide control period to 146.6 seconds after breathing carbon monoxide (P less than 0.001). The mean exercise time was 219.9 seconds in the air control period and 221.3 seconds after purified air (P not significant). Breathing 100 ppm of carbon monoxide for 1 hour caused a significant reduction in exercise performance in patients with chronic obstructive pulmonary disease.     

Inspiratory capacity predicts mortality in patients with chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) severity is usually graded upon the FEV(1) reduction and FEV(1) has been considered the most important mortality predictor with age in COPD. Recent studies suggest other factors as more powerfully related to mortality than FEV(1) in COPD patients. AIM: To assess the impact of inspiratory capacity (IC) on mortality and morbidity in COPD patients during a 5-year follow-up period. METHODS: We recruited 222 patients with mild-to-moderate COPD from January 1995 to December 2001 with an average follow-up period of 60 months (range 30-114 months). Among different respiratory parameters measured in stable conditions FEV(1), FEV(1)/FVC%, IC and PaO(2), PaCO(2) and BMI were chosen and their relationships with all-cause and respiratory mortality and with morbidity were assessed. RESULTS: All these variables were associated with mortality at the univariate analysis. However, in a multivariate regression analysis (Cox proportional hazards model) for all-cause mortality age (year), IC (%pred.) and PaO(2) (mmHg) remained the only significant, independent predictors (HR=1.056, 95%CI: 1.023-1.091; HR=0.981, 95%CI: 0.965-0.998; HR=0.948, 95%CI: 0.919-0.979, respectively). According to the same analysis, IC (%pred.) and PaO(2) (mmHg) were significant independent predictors for respiratory mortality (HR=0.967, 95%CI: 0.938-0.997; HR=0.919, 95%CI: 0.873-0.969) together with FEV(1)/FVC% and BMI (kg/m(2)) (HR=0.967, 95%CI: 0.933-1.022; HR=0.891, 95%CI: 0.807-0.985, respectively). IC (%pred.), FEV(1)/FVC%, and PaO(2) (mmHg) were also significantly related to morbidity, as independent predictors of hospital admissions because of exacerbations (OR=0.980, 95%CI: 0.974-0.992; OR=0.943, 95%CI: 0.922-0.987; OR=0.971, 95%CI: 0.954-0.996, respectively). CONCLUSION: IC (%pred.) is a powerful functional predictor of all-cause and respiratory mortality and of exacerbation-related hospital admissions in COPD patients.     

Evolution of changes in carbon monoxide transfer factor in men with chronic obstructive pulmonary disease

Progression of chronic obstructive pulmonary disease (COPD) has been studied predominantly by following change in forced expiratory volume in 1s (FEV1) which reflects both primary airway disease and associated alveolar disease. Carbon monoxide transfer (Tlco) (the product of the transfer coefficient Kco and alveolar volume Va) is the only simple, widely available test of alveolar function, but few studies have followed long-term changes in an individual. Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1 56% of predicted values) were observed with yearly measurements of FEV1, Tlco and Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of predicted values. Va, measured by single breath dilution, fell in each man. Kco at recruitment ranged from 41% to 110% predicted and remained >75% predicted in eight men at the end of follow-up supporting a phenotype of COPD with predominant airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO transfer in an individual should increase the present poor knowledge of the contribution of alveolar disease to the progression of chronic airflow obstruction.     

稳定期COPD患者深吸气量与运动耐力的关系

目的 探讨深吸气量 (IC)及相关肺功能指标与稳定期中重度 COPD患者运动耐力的相关性.方法 对62例处于稳定期的中重度 COPD 患者进行常规肺功能检测及斜坡式功率递增症状限制性心肺运动试验,测定相关肺通气功能参数、气体交换参数.结果 COPD患者的 IC%pred与运动耐力 [峰值摄氧量占预计值的百分比 (peak ·V O2%pred)]有显著的相关性 (r =0.74,P <0.001),IC%pred对 peak ·V O2%pred 有显著预测意义.结论 IC%pred对稳定期 COPD患者运动耐力的预测较其他肺功能指标更有优势.     

Effect of chlormadinone acetate on ventilatory control in patients with chronic obstructive pulmonary disease

Twelve patients with chronic obstructive pulmonary disease (COPD) were studied to determine the effect of ventilatory stimulation with chlormadinone acetate (CMA), a potent synthetic progesterone, on chemical and neuromechanical respiratory controls and pulmonary gas exchange. Using a randomized, double-blind, cross-over trial, 1 wk of CMA therapy caused a significant reduction in arterial CO2 tension (Paco2) by 4.6 +/- 0.6 (SE) mmHg. This Paco2 fall was associated with increased minute ventilation (Vl), tidal volume (VT), and mean inspiratory flow (VT/Tl). During CMA administration, occlusion pressure response to CO2 with and without inspiratory flow-resistive loading increased significantly (p less than 0.01) over that during placebo administration, whereas ventilatory response to CO2 did not. In addition, normocapnic ventilatory and occlusion pressure response to hypoxia were significantly elevated (p less than 0.01) during CMA therapy. Furthermore, the degree of load compensation, which was assessed by the ratio of the loaded to unloaded slope in the occlusion pressure response to CO2, increased in all subjects after CMA administration. These results indicate that CMA augments not only the respiratory neuromuscular response to hypercapnia and hypoxia, but also flow-resistive load compensation in patients with COPD, and it may provide support for the use of CMA in patients who are able to decrease their Paco2 with this agent.     

Effect of bronchodilatation on single breath pulmonary uptake of carbon monoxide in chronic obstructive pulmonary disease

We studied 21 COPD patients in stable clinical conditions to evaluate whether changes in lung function induced by cumulative doses of salbutamol alter diffusing capacity for carbon monoxide (DL_CO), and whether this relates to the extent of emphysema as assessed by high resolution computed tomography (HRCT) quantitative analysis. Spirometry and DL_CO were measured before and after cumulative doses of inhaled salbutamol (from 200 μg to 1000 μg). Salbutamol caused significant increments of forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and flows at 30% of control FVC taken from both partial and maximal forced expiratory maneuvers. Functional residual capacity and residual volume were reduced, while total lung capacity did not change significantly. DL_CO increased progressively with the incremental doses of salbutamol, but this became significant only at the highest dose (1000 μg) and was independent of the extent of emphysema, as assessed by radiological parameters. No significant changes were observed in CO transfer factor (DLCO/VA) and alveolar volume (VA). The results suggest that changes in lung function induced by cumulative doses of inhaled salbutamol are associated with a slight but significant increase in DL_CO irrespective of the presence and extent of emphysema.     

慢性阻塞性肺疾病患者运动能力与通气效率的相关性分析

目的:通过分析二氧化碳通气当量和运动能力的关系,探讨稳定期慢性阻塞性肺疾病(COPD)患者运动中通气效率与最大运动能力的相关性。方法:选取54例稳定期COPD患者,行运动心肺功能测试,实时监测摄氧量(VO2)、分钟通气量(VE)和二氧化碳排出量(VCO2),根据公式:EqCO2=VE/VCO2计算得出静态二氧化碳通气当量(EqCO2rest)、无氧阈时二氧化碳通气当量(EqCO2at)和最大运动状态下的二氧化碳通气当量(EqCO2max)。结果:1.EqCO2rest、EqCO2at及EqCO2max呈递减趋势,差异有统计学意义(P=0.001)。2.EqCO2at与最大摄氧量(VO2max)(r=-0.294,P<0.05)、EqCO2max与VO2max(r=-0.301,P<0.05)均呈负相关;EqCO2rest与最大摄氧量占预计值的百分比(VO2max/Pred)呈负相关(r=-0.345,P<0.05)。3.肺功能GOLD 3级患者(21例)的VO2max(15.99±3.39)mL·min-1·kg-1明显低于GOLD 2级患者(25例)的VO2max[(18.88±5.36)mL·min-1·kg-1,P=0.038]。两组的EqCO2rest、EqCO2at及EqCO2max差异无统计学意义。结论:稳定期COPD患者运动中通气效率呈进行性下降趋势,这可能是导致其运动能力下降的重要因素之一。     

Rehabilitation for patients with chronic obstructive pulmonary disease

OBJECTIVE: To develop a meta-analysis to determine the effectiveness of rehabilitation in patients with chronic obstructive pulmonary disease (COPD). DATA SOURCES: medline, cinhal, and Cochrane Library searches for trials of rehabilitation for COPD patients. Abstracts presented at national meetings and the reference lists of pertinent articles were reviewed. STUDY SELECTION: Studies were included if: trials were randomized; patients were symptomatic with forced expiratory volume in one second (FEV1) <70% or FEV1 divided by forced vital capacity (FEV1/FVC) <70% predicted; rehabilitation group received at least 4 weeks of rehabilitation; control group received no rehabilitation; and outcome measures included exercise capacity or shortness of breath. We identified 69 trials, of which 20 trials were included in the final analysis. DATA EXTRACTION: Effect of rehabilitation was calculated as the standardized effect size (ES) using random effects estimation techniques. RESULTS: The rehabilitation groups of 20 trials (979 patients) did significantly better than control groups on walking test (ES = 0.71; 95% confidence interval [95% CI], 0.43 to 0.99). The rehabilitation groups of 12 trials (723 patients) that used the Chronic Respiratory Disease Questionnaire had less shortness of breath than did the control groups (ES = 0.62; 95% CI, 0.35 to 0.89). Trials that used respiratory muscle training only showed no significant difference between rehabilitation and control groups, whereas trials that used at least lower-extremity training showed that rehabilitation groups did significantly better than control groups on walking test and shortness of breath. Trials that included severe COPD patients showed that rehabilitation groups did significantly better than control groups only when the rehabilitation programs were 6 months or longer. Trials that included mild/moderate COPD patients showed that rehabilitation groups did significantly better than control groups with both short- and long-term rehabilitation programs. CONCLUSION: COPD patients who receive rehabilitation have a better exercise capacity and they experience less shortness of breath than patients who do not receive rehabilitation. COPD patients may benefit from rehabilitation programs that include at least lower-extremity training. Patients with mild/moderate COPD benefit from short- and long-term rehabilitation, whereas patients with severe COPD may benefit from rehabilitation programs of at least 6 months.     

深吸气量的测定在慢性阻塞性肺疾病患者中的临床意义

目的探讨肺功能指标深吸气量的测定在慢性阻塞性肺疾病患者中的临床应用价值。方法对21例COPD患者肺功能测定和支气管舒张试验,比较吸入沙丁胺醇200μg前后各肺功能指标的变化,并比较各指标在支气管扩张试验阳性组与阴性组、阻塞程度较中度组与重一极重度组的组中和组间差异性。结果在各项肺功能指标中,仅IC、FVC和FEV1在吸药后增加,其中IC的增加幅度最大。舒张试验阳性组和阴性组IC皆明显增加,且增加幅度相似。IC的增加幅度在重—极重度组大于轻—中度组。结论IC的增加与舒张试验的阳性和阴性结果没有必然的关联,可作为独立指标。支气管扩张剂缓解呼吸困难症状和增加运动耐力的作用在阻塞程度较重者更明显。     

Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease

Static lung hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease. We analyzed the power of lung hyperinflation as measured by the inspiratory capacity-to-total lung capacity ratio (IC/TLC) to predict mortality in a cohort of 689 patients with chronic obstructive pulmonary disease (95% males; FEV(1), 1.17 L) with a mean follow-up of 34 months. We also compared the predictive value of IC/TLC with that of the BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index. Subjects who died (183; 27%) were older; had lower body mass index, FEV(1), and IC/TLC ratio; walked less in the 6-minute walking distance; and had more dyspnea, a higher BODE Index, and comorbidity (p < 0.001). On the basis of logistic regression analysis, IC/TLC was found to be a good and independent predictor of all-cause and respiratory mortality. On the basis of receiver operating characteristic Type II curves, IC/TLC compared favorably with FEV(1) and predicted mortality independently of the BODE Index. We conclude that IC/TLC is an independent risk factor for mortality in subjects with chronic obstructive pulmonary disease. We propose that this ratio be considered in the assessment of patients with chronic obstructive pulmonary disease.