Ventilatory and metabolic adaptations to walking and cycling in patients with COPD.

To test the hypothesis that in chronic obstructive pulmonary disease (COPD) patients the ventilatory and metabolic requirements during cycling and walking exercise are different, paralleling the level of breathlessness, we studied nine patients with moderate to severe, stable COPD. Each subject underwent two exercise protocols: a 1-min incremental cycle ergometer exercise (C) and a "shuttle" walking test (W). Oxygen uptake (VO(2)), CO(2) output (VCO(2)), minute ventilation (VE), and heart rate (HR) were measured with a portable telemetric system. Venous blood lactates were monitored. Measurements of arterial blood gases and pH were obtained in seven patients. Physiological dead space-tidal volume ratio (VD/VT) was computed. At peak exercise, W vs. C VO(2), VE, and HR values were similar, whereas VCO(2) (848 +/- 69 vs. 1,225 +/- 45 ml/min; P < 0. 001) and lactate (1.5 +/- 0.2 vs. 4.1 +/- 0.2 meq/l; P < 0.001) were lower, DeltaVE/DeltaVCO(2) (35.7 +/- 1.7 vs. 25.9 +/- 1.3; P < 0. 001) and DeltaHR/DeltaVO(2) values (51 +/- 3 vs. 40 +/- 4; P < 0.05) were significantly higher. Analyses of arterial blood gases at peak exercise revealed higher VD/VT and lower arterial partial pressure of oxygen values for W compared with C. In COPD, reduced walking capacity is associated with an excessively high ventilatory demand. Decreased pulmonary gas exchange efficiency and arterial hypoxemia are likely to be responsible for the observed findings.     

Determinants of elevated healthcare utilization in patients with COPD

Background

Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems. Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.

Methods

Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency. Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database. Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.

Results

Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001). The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs. Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6). Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.

Conclusion

Comorbidity burden determines elevated utilization for COPD patients. Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients.     

清脑复神液治疗COPD失眠的临床观察

目的:观察中成药清脑复神液(四川中方制药)对COPD失眠的疗效及对呼吸中枢的安全性;方法:将88例病人随机分为2组:治疗组48人给予口服清脑复神液20ml,每日两次治疗,对照组每晚口服VitB1片10mg,共7d.阿森斯失眠量表(AIS)判定疗效,同时查血气分析测定PaO2、PaCO2.结果:治疗组治疗后AIS评分与治疗前比较明显降低(P＜0.01),两组治疗后AIS评分存在显著差异(P＜0.01);对照组治疗前后AIS评分无明显差异(P＞0.05),两组病人治疗后PaO2、PaCO2无明显差异(P＞0.05).结论:清脑复神液能改善COPD失眠患者的睡眠质量,且对COPD患者无明显呼吸抑制作用.     

高频通气膈肌起搏对COPD病人血气,呼吸肌功能,膈肌活动度和潮气量的影响

目的观察高频通气膈肌起搏（ＨＤＰ）对慢性阻塞性肺病（ＣＯＰＤ）治疗作用。方法１９例ＣＯＰＤ病人给予ＨＤＰ治疗。结果ＨＤＰ可增加伴有或不伴有呼吸衰竭的ＣＯＰＤ患者ＰａＣＯ２、ＳａｔＯ２膈肌活动度和潮气量,而对ＰａＣＯ２、口腔最大吸气压、口腔最大呼气压无明显的影响。结论ＨＤＰ对ＣＯＰＤ有较好的治疗作用,短时治疗对呼吸肌功能无明显的影响。     

Airway wall thickness is increased in COPD patients with bronchodilator responsiveness

Rationale

Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD. The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described. We aimed to assess airway dimensions in COPD subjects with and without BDR.

Methods

We analyzed subjects with GOLD 1–4 disease in the COPDGene® study who had CT airway analysis. We divided patients into two groups: BDR + (post bronchodilator ΔFEV₁ ≥ 10%) and BDR-(post bronchodilator ΔFEV₁ < 10%). The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA. Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter. %Emphysema and %gas trapping were also calculated.

Results

2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis. The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group. In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV₁, and %predicted FVC, airway wall measures remained independent predictors of BDR. Using a threshold change in FEV₁ ≥ 15% and FEV₁ ≥ 12% and 200 mL to divide patients into groups, the results were similar.

Conclusion

BDR in COPD is independently associated with CT evidence of airway pathology. This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD.     

慢性阻塞性肺疾病合并糖尿病患者口腔菌群及肠道菌群的研究

探讨慢性阻塞性肺疾病(COPD)合并糖尿病患者与糖尿病患者口腔菌群及肠道菌群的差异。

选取2019年5月到2020年5月于我院就诊的COPD合并糖尿病患者与仅患糖尿病的患者各30例。检测两组患者的各项身体指标以及生化指标。采集两组患者牙体颊/舌面液体, 提取细菌基因组DNA, 采用荧光定量PCR鉴定常见口腔细菌。采用贴纸收集粪便样本, 并用选择性琼脂培养基培养菌群, 结果以每毫升粪便的菌落形成单位(CFU)表示。通过BBL Crystal^TM鉴定系统对分离出的细菌进行鉴定。采用Elisa试剂盒测量粪便中Zonulin的水平(ng/mL)。

COPD合并糖尿病患者体质量指数[(29.54±2.16)kg/m²]较高, 血糖水平也较高, 但与糖尿病组比较差异无统计学意义(均P＞0.05)。COPD合并糖尿病患者CRP水平升高(P＜0.05), 其他各项指标两组间差异无统计学意义(均P＞0.05)。30例COPD合并糖尿病患者链球菌检出率为60.0%, 奈瑟菌检出率为30.0%, 放线菌检出率为66.7%, 韦荣球菌检出率为40.0%, 牙龈卟啉单胞菌的检出率为70.0%。30例糖尿病患者链球菌检出率为40.0%, 奈瑟菌检出率为56.7%, 放线菌检出率为36.7%, 韦荣球菌检出率为73.3%, 牙龈卟啉单胞菌的检出率为46.7%。Zonulin与炎症和真菌数量之间存在显著正相关。

COPD合并糖尿病患者肠道真菌数量、肠屏障功能与全身性炎症之间存在密切联系。

     

Impact of heterozygote CFTR Mutations in COPD patients with Chronic Bronchitis

Background

Cigarette smoking causes Chronic Obstructive Pulmonary Disease (COPD), the 3rd leading cause of death in the U.S. CFTR ion transport dysfunction has been implicated in COPD pathogenesis, and is associated with chronic bronchitis. However, susceptibility to smoke induced lung injury is variable and the underlying genetic contributors remain unclear. We hypothesized that presence of CFTR mutation heterozygosity may alter susceptibility to cigarette smoke induced CFTR dysfunction. Consequently, COPD patients with chronic bronchitis may have a higher rate of CFTR mutations compared to the general population.

Methods

Primary human bronchial epithelial cells derived from F508del CFTR heterozygotes and mice with (CFTR+/-) and without (CFTR+/+) CFTR heterozygosity were exposed to whole cigarette smoke (WCS); CFTR-dependent ion transport was assessed by Ussing chamber electrophysiology and nasal potential difference measurements, respectively. Caucasians with COPD and chronic bronchitis, age 40 to 80 with FEV₁/FVC < 0.70 and FEV₁ < 60% predicted, were selected for genetic analysis from participants in the NIH COPD Clinical Research Network’s Azithromycin for Prevention of Exacerbations of COPD in comparison to 32,900 Caucasian women who underwent prenatal genetic testing. Genetic analysis involved an allele-specific genotyping of 89 CFTR mutations.

Results

Exposure to WCS caused a pronounced reduction in CFTR activity in both CFTR (+/+) cells and F508del CFTR (+/-) cells; however, neither the degree of decrement (44.7% wild-type vs. 53.5% F508del heterozygous, P = NS) nor the residual CFTR activity were altered by CFTR heterozygosity. Similarly, WCS caused a marked reduction in CFTR activity measured by NPD in both wild type and CFTR heterozygous mice, but the severity of decrement (91.1% wild type vs. 47.7% CF heterozygous, P = NS) and the residual activity were not significantly affected by CFTR genetic status. Five of 127 (3.9%) COPD patients with chronic bronchitis were heterozygous for CFTR mutations which was not significantly different from controls (4.5%) (P = NS).

Conclusions

The magnitude of WCS induced reductions in CFTR activity was not affected by the presence of CFTR mutation heterozygosity. CFTR mutations do not increase the risk of COPD with chronic bronchitis. CFTR dysfunction due to smoking is primarily an acquired phenomenon and is not affected by the presence of congenital CFTR mutations.     

Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea

Background

Exercise limitation is an important issue in patients with chronic obstructive pulmonary disease (COPD), and it often co-exists with obstructive sleep apnoea (overlap syndrome). This study examined the effects of nocturnal continuous positive airway pressure (CPAP) treatment on walking capacity in COPD patients with or without obstructive sleep apnoea.

Methods

Forty-four stable moderate-to-severe COPD patients were recruited and completed this study. They all underwent polysomnography, CPAP titration, accommodation, and treatment with adequate pressure. The incremental shuttle walking test was used to measure walking capacity at baseline and after two nights of CPAP treatment. Urinary catecholamine and heart rate variability were measured before and after CPAP treatment.

Results

After two nights of CPAP treatment, the apnoea-hypopnoea index and oxygen desaturation index significantly improved in both overlap syndrome and COPD patients, however these changes were significantly greater in the overlap syndrome than in the COPD group. Sleep architecture and autonomic dysfunction significantly improved in the overlap syndrome group but not in the COPD group. CPAP treatment was associated with an increased walking capacity from baseline from 226.4 ± 95.3 m to 288.6 ± 94.6 m (P < 0.05), and decreased urinary catecholamine levels, pre-exercise heart rate, oxygenation, and Borg scale in the overlap syndrome group. An improvement in the apnoea-hypopnoea index was an independent factor associated with the increase in walking distance (r = 0.564).

Conclusion

Nocturnal CPAP may improve walking capacity in COPD patients with overlap syndrome.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT00914264","term_id":"NCT00914264"}}NCT00914264     

脉冲振荡测定COPD患者呼吸阻抗的临床意义

通过对40名COPD患者，30名健康者，以德国Master sereen PFT肺功能仪对其进行呼吸阻抗测定，并与常规肺功能比较，探讨脉冲振荡法在COPD患者中的应用。     

Inflammatory cells and apoptosis in respiratory and limb muscles of patients with COPD

Discrepancies exist regarding the involvement of cellular inflammation and apoptosis in the muscle dysfunction of chronic obstructive pulmonary disease (COPD) patients with preserved body composition. We explored whether levels of inflammatory cells and apoptosis were increased in both respiratory and limb muscles of COPD patients without nutritional abnormalities. In the vastus lateralis, external intercostals, and diaphragms of severe and moderate COPD patients with normal body composition, and in healthy subjects, intramuscular leukocytes and macrophage levels were determined (immunohistochemistry). Muscle structure was also evaluated. In the diaphragm and vastus lateralis of severe and moderate COPD patients and controls, apoptotic nuclei were explored using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, electron microscopy, and caspase-3 expression. In COPD patients compared with controls, diaphragm and intercostal levels of inflammatory cells were extremely low and not significantly different. However, in the vastus lateralis of the severe patients, inflammatory cell counts, although also very low, were significantly greater. In those patients, TUNEL-positive nuclei levels were also significantly greater in diaphragms and vastus lateralis. A significant inverse relationship was found between quadriceps TUNEL-positive nuclei levels and muscle force. Ultrastructural apoptotic nuclei revealed no differences in respiratory or limb muscles between COPD patients and controls. Muscle caspase-3 expression did not differ between patients and controls. In severe COPD patients with preserved body composition, while increased apoptotic nuclei seems to be a contributor to their muscle dysfunction, cellular inflammation does not. The increased numbers of TUNEL-positive nuclei in their muscles suggest that they may also be exposed to a continuous repair/remodeling process.     

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

Background

Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population.

Methods

The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications.

Results

Seven polymorphisms were found being associated with risk of asthma, namely: A Disintegrin and Metalloprotease 33 (ADAM33) T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73), Angiotensin-Converting Enzyme (ACE) D/I (OR = 3.85, 95%CI: 2.49-5.94), High-affinity IgE receptor β chain (FcεRIβ) -6843G/A (OR = 1.49, 95%CI: 1.01-2.22), Interleukin 13(IL-13) -1923C/T (OR = 2.99, 95%CI: 2.12-4.24), IL-13 -2044A/G (OR = 1.49, 95%CI: 1.07-2.08), Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) -28C/G (OR = 1.64, 95%CI: 1.09-2.46), Tumor Necrosis Factor-α (TNF-α) -308G/A(OR = 1.42, 95%CI: 1.09, 1.85). After subgroup analysis by age, the ACE D/I, β2-Adrenergic Receptor (β2-AR) -79G/C, TNF-α -308G/A, Interleukin 4 receptor(IL-4R) -1902G/A and IL-13 -1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the ACE D/I, FcεRIβ -6843G/A, TNF-α -308G/A, IL-13 -1923C/T and IL-13 -2044A/G polymorphisms were associated with asthma risk in Chinese adults.

Conclusion

ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R and IL-13 genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.     

Sleep related O2 desaturation in COPD patients with normoxaemia and mild hypoxyaemia

It is unknown whether daytime features predict oxygenation during sleep in COPD patients with normoxaemia or mild hypoxaemia. In this study our purpose was to evaluate by a pulse oxymeter, nocturnal desaturation in 33 COPD with PaO2 > 60 mmHg and to examine some daytime parameters as possible predictors of nocturnal hypoxaemia. A significant nocturnal desaturation has been defined by spending > or = 30% of total sleep-time with a TSTSaO2 < 90% > 30. According to this criterion we classified our patients in Desaturators (D) and Non Desaturators (ND). Our results showed that 39% of our patients were D and 61% ND. Among anthropometric and respiratory functional data we found that daytime SaO2B (r = 0.74 p < 0.001) daytime PaO2 (r = 0.47 p < 0.01) and daytime PaCO2 (r = 0.45 p < 0.05) were significantly correlated with the nocturnal oxygen desaturation and can predict the presence of sleep related hypoxaemia. In conclusion, our study confirms that a relatively high percentage of COPD patients with normoxaemia or borderline hypoxaemia exhibits significant nocturnal hypoxaemia. Further studies will suggest whether sleep related hypoxaemia deserves nocturnal oxygen therapy.     

Mechanisms for isolated volume response to a bronchodilator in patients with COPD.

We hypothesized that an altered effect of lung inflation on airway caliber may in part explain the isolated volume response to bronchodilators, i.e., an increase of forced vital capacity (FVC) without change in 1-s forced expiratory volume (FEV(1)). Small-airway caliber was measured by high-resolution computed tomography at functional residual capacity and total lung capacity in five chronic obstructive pulmonary disease patients with an isolated increase of FVC (FVC responders) and five with an increase of both FVC and FEV(1) (FVC-FEV(1) responders) after inhalation of salbutamol. In FVC-FEV(1) responders, the airway diameter increased with the cube root of increase in lung volume but was unchanged or even decreased in four of five FVC responders. FVC responders had more severe emphysema, as inferred from lung function and imaging studies, than FVC-FEV(1) responders. We speculate that longitudinal traction or space competition (Verbeken EK, Cauberghs M, and Van de Woestijne KP, J Appl Physiol 81: 2468-2480, 1996) are possible underlying mechanisms. We conclude that the isolated volume response to bronchodilators is associated with severe emphysema and likely results from an altered effect of lung inflation on airway caliber.