Sex differences in exertional dyspnea in patients with mild COPD: physiological mechanisms

The purpose of this study was to evaluate the physiological basis for sex-differences in exercise-induced dyspnea in patients with mild COPD. We compared operating lung volumes, breathing pattern and dyspnea during incremental cycling in 32 men (FEV(1)=86±10% predicted) and women (FEV(1)=86±12% predicted) with mild COPD and 32 age-matched controls. There were no sex differences in dyspnea in the control group at any work-rate or ventilation (V(E)). Women with COPD had significantly greater dyspnea than men at 60 and 80 W. At 80 W, dyspnea ratings were 5.7±2.3 and 3.3±2.5 Borg units (P<0.05) and the V(E) to maximal ventilatory capacity ratio was 72% and 55% in women and men, respectively (P<0.05). Comparable increases in dynamic hyperinflation were seen in both male and female COPD groups at symptom limitation but women reached tidal volume constraints at a lower work rate and V(E) than men. Superimposing mild COPD on the normal aging effects had greater sensory consequences in women because of their naturally reduced ventilatory reserve.     

Evaluation of Quality of Life with the Chronic Obstructive Pulmonary Disease Assessment Test in Chronic Obstructive Pulmonary Disease and the Effect of Dyspnea on Disease-Specific Quality of Life in These Patients

Purpose

The chronic obstructive pulmonary disease (COPD) assessment test (CAT) was recently introduced for use in assessing disease-specific quality of life and follow-up of patients with COPD. The purpose of this study was to evaluate the effect of the dyspnea on disease-specific quality of life detected by CAT score in patients with COPD.

Materials and Methods

In this study, 90 stable patients with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were included. The level of dyspnea was assessed with the Medical Research Council (MRC) dyspnea scale, and disease-specific quality of life was assessed with CAT score.

Results

The mean±SD age was 68.5±10.9 (range 41-97) years. A significant relationship was established between CAT score, MRC dyspnea scale score and GOLD stage in patients with COPD. There was also a positive correlation between dyspnea scale scores and GOLD stage in the patients (p<0.001), as well as positive correlation between CAT score and dyspnea scale score (p<0.001). CAT score showed a significant correlation with hospitalization and exacerbations (p<0.05).

Conclusion

Dyspnea is an important symptom that may impact quality of life in patients with COPD. CAT was shown to be a simple, fast and intelligible measurement of disease-specific quality of life, and was correlated with levels of dyspnea in patients with COPD.     

Too rapid increase and too much breathlessness are distinct indices of exertional dyspnea in COPD

To assess whether different indices of dyspnea can be obtained from cardiopulmonary exercise test and whether these indices correlate with distinct physiological parameters in COPD. Forty-two COPD patients (12 females, median [IQ] age 66 [56-70] years; FEV(1)% predicted: 51 [38-65]) underwent pulmonary function and incremental exercise tests. A power law function described the oxygen consumption (V(O?)-Dyspnea relationship from which two indices correlated with MRC score: dyspnea score measured at 50% of predicted V(O?) (too much breathless for that effort) and tangent measured at 50% of peak dyspnea (too rapid increase in dyspnea at this time point). The former independently correlated with ventilation on exercise, while the latter independently correlated with baseline hyperinflation. An upward shift of both (iso)-V(O?) and -ventilation was evidenced in patients with higher levels of dyspnea (MRC score ≥ 3) and their tangents were significantly different. In conclusion, baseline hyperinflation is associated with the perception of a too rapid increase in dyspnea on exercise in COPD.     

Effects of thoracic kinesio taping on pulmonary functions,respiratory muscle strength and functional capacity in patients with chronic obstructive pulmonary disease: A randomized controlled trial

ContextRespiratory and peripheral muscle dysfunctions seen in Chronic Obstructive Pulmonary Disease (COPD) cause ventilatory limitation, dyspnea and inactivity, which then result in a reduction in functional capacity. Kinesio Taping (KT) is a rehabilitative technique performed by the cutaneous application of a special elastic tape, thus increasing muscle activation and blood circulation.ObjectivesTo investigate the effects of KT application that was applied on respiratory muscles to improve pulmonary function, respiratory muscle strength and functional capacity in patients with COPD.Patients and methodsIn total, 27 COPD patients (16 in KT group, 11 in control group) were included. Thoracic KT was applied to facilitate the respiratory muscles along the subcostal area for KT group. Deep breathing exercises were applied to both groups. Interventions were done 2 days a week, through 6 weeks. Pulmonary function and maximal respiratory mouth pressures were measured with a spirometer. Severity of dyspnea and fatigue were assessed with Modified Medical Research Council dyspnea scale and Modified Borg Scale, respectively. Functional capacity was evaluated using six-minute walk test.ResultsPercentage predicted of forced expiratory volume in one second (FEV₁%), peak expiratory flow (PEF) value, percentage predicted of peak expiratory flow (PEF%) and walking distance were significantly increased in KT group (p = 0.038, p = 0.011, p = 0.013, p = 0.004, respectively). The severity of dyspnea and fatigue were reduced in KT group (p < 0.05). There was no significant change for other variables in-group and between-group analyses (p > 0.05).ConclusionsThoracic KT may be beneficial for improving pulmonary function and functional capacity in patients with COPD.     

呼吸训练联合膈肌起搏器治疗慢性阻塞性肺疾病的优化肺康复模式研究

【摘要】目的:探讨呼吸训练联合膈肌起搏器治疗慢性阻塞性肺疾病（COPD）的优化肺康复模式效果。方法:前瞻性非随机收集2017年9月~2019年3月长沙市第四医院呼吸内科及康复医学科收治的中度至极重度稳定期COPD患者88例,按照患者意愿分为A、B、C、D组,A组采用常规内科治疗+呼吸训练,B组采用常规内科治疗+膈肌起搏器,C组采用常规内科治疗+呼吸训练+膈肌起搏器,D组采用单纯常规内科治疗。分析2个月后各组肺功能、6 min步行试验（6MWT）结果、呼吸困难量表（MRC）评分、圣乔治呼吸问卷（SGRQ）评分情况。结果:C组第1秒末用力呼气容量（FEV1）、FEV1/用力肺活量（FVC）及最大通气量（MVV）水平显著高于A、B、D组,FVC水平显著高于A组和D组（P<0.05）;C组6MWT显著高于其他各组,Borg疲劳评分、Borg喘息评分均显著低于其他各组（P<0.05）;C组MRC评分显著低于D组（P<0.05）;C组症状、日常活动情况、疾病影响评分均显著高于其余3组（P<0.05）。结论:呼吸训练联合膈肌起搏器治疗COPD能够有效改善患者肺功能,缓解其呼吸困难情况,并提高其生活质量及运动耐力,取得最佳肺康复疗效。 【关键词】呼吸训练;膈肌起搏器;慢性阻塞性肺疾病;肺康复     

Ventilatory responses to exercise training in obese adolescents

The aim of this study was to examine ventilatory responses to training in obese adolescents. We assessed body composition, pulmonary function and ventilatory responses (among which expiratory flow limitation and operational lung volumes) during progressive cycling exercise in 16 obese adolescents (OB) before and after 12 weeks of exercise training and in 16 normal-weight volunteers. As expected, obese adolescents' resting expiratory reserve volume was lower and inversely correlated with thoraco-abdominal fat mass (r=-0.74, p<0.0001). OB presented lower end expiratory (EELV) and end inspiratory lung volumes (EILV) at rest and during submaximal exercise, and modest expiratory flow limitation. After training, OB increased maximal aerobic performance (+19%) and maximal inspiratory pressure (93.7±31.4 vs 81.9±28.2cmH(2)O, +14%) despite lack of decrease in trunk fat and body weight. Furthermore, EELV and EILV were greater during submaximal exercise (+11% and +9% in EELV and EILV, respectively), expiratory flow limitation delayed but was not accompanied by increased V(T). However, submaximal exertional symptoms (dyspnea and leg discomfort) were significantly decreased (-71.3% and -70.7%, respectively). Our results suggest that exercise training can improve pulmonary function at rest (static inspiratory muscle strength) and exercise (greater operating lung volumes and delayed expiratory flow limitation) but these modifications did not entirely account for improved dyspnea and exercise performance in obese adolescents.     

Genome-wide association analysis of body mass in chronic obstructive pulmonary disease

Cachexia, whether assessed by body mass index (BMI) or fat-free mass index (FFMI), affects a significant proportion of patients with chronic obstructive pulmonary disease (COPD), and is an independent risk factor for increased mortality, increased emphysema, and more severe airflow obstruction. The variable development of cachexia among patients with COPD suggests a role for genetic susceptibility. The objective of the present study was to determine genetic susceptibility loci involved in the development of low BMI and FFMI in subjects with COPD. A genome-wide association study (GWAS) of BMI was conducted in three independent cohorts of European descent with Global Initiative for Chronic Obstructive Lung Disease stage II or higher COPD: Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points (ECLIPSE; n = 1,734); Norway-Bergen cohort (n = 851); and a subset of subjects from the National Emphysema Treatment Trial (NETT; n = 365). A genome-wide association of FFMI was conducted in two of the cohorts (ECLIPSE and Norway). In the combined analyses, a significant association was found between rs8050136, located in the first intron of the fat mass and obesity-associated (FTO) gene, and BMI (P = 4.97 × 10(-7)) and FFMI (P = 1.19 × 10(-7)). We replicated the association in a fourth, independent cohort consisting of 502 subjects with COPD from COPDGene (P = 6 × 10(-3)). Within the largest contributing cohort of our analysis, lung function, as assessed by forced expiratory volume at 1 second, varied significantly by FTO genotype. Our analysis suggests a potential role for the FTO locus in the determination of anthropomorphic measures associated with COPD.     

The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with Chronic Obstructive Pulmonary Disease

The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was defined as RV/TLC ≥ 40%. Multivariate logistic regression analysis demonstrated that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV₁) (P < 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019), and higher emphysema index (P = 0.010) were associated independently with resting hyperinflation. Multivariate Cox regression model that included age, gender, dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter 6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all-cause mortality. Our data showed that older age, higher emphysema index, higher SGRQ score, and lower FEV₁ were associated independently with resting pulmonary hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause mortality in COPD.

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Lung tissue and tumour-infiltrating T lymphocytes in patients with non-small cell lung carcinoma and chronic obstructive pulmonary disease (COPD): moderate/severe versus mild stage of COPD

Cytotoxic CD8+ T cells have been suggested to be key players in the pathogenesis of chronic obstructive pulmonary disease (COPD). We wanted to investigate the phenotype of lung tissue T lymphocytes (LTL) and tumour-infiltrating T lymphocytes (TIL) in smokers with peripheral non-small cell lung carcinoma (NSCLC) with moderate/severe versus mild COPD. Lung tissue and tumour samples were obtained from patients with moderate/severe stage of COPD (n = 10) and from patients with mild stage of COPD (n = 7) at lung resection for a solitary peripheral NSCLC, processed and analysed by flow cytometry. The flow-cytometric results showed that lung tissue T cells, regardless of the severity of COPD, were mostly of the activated phenotype, expressed the CXCR3 chemokine receptor characteristic of type 1 T cells, and did neither significantly differ in the expression of activation markers (CD69, CD25 and HLA-DR), differentiation markers (CD27 and CD28) and chemokine receptors (CXCR3 and CCR4) between the selected groups, nor showed any significant correlation with lung function measured as forced expiratory volume in 1 s (FEV1) or TLCO. Compared with LTL, a significantly greater proportion of TIL expressed the activation markers CD69 and CD25, but a lower proportion showed a fully differentiated CD27- 28- phenotype. We conclude that lung LTL patterns are similar in NSCLC patients with moderate/severe or mild stages of COPD, and are not significantly related to lung function. LTL and TIL possess different phenotype characteristics. The majority of tumour tissue T cells are activated, but it seems that their process of differentiation is incomplete.     

Noninvasive measurement of regional lung water distribution in healthy man and in pulmonary oedema

A quasi steady-state noninvasive, radioisotopic technique for measuring regional lung water distribution in man is described. The method depends upon the dilution principle. 123I labelled human serum albumin (HSA) and sodium iodide (NaI) were injected intravenously, allowed to mix completely within the body fluids and then counted externally over the chest. The size of each compartment to which the markers are confined was calculated from the external count rate and the isotopic concentration of the marker in plasma. 123I-HSA was used to estimate intravascular water and 123I-NaI extracellular water. Ratio analysis of the differential attenuation of the two photoenergies of 123Iodine (29 keV, 159 keV) by the lung and chest wall was used to estimate the absolute amount of isotope in the lung, independent of chest wall contribution, after validation by phantom studies. Regional pulmonary plasma (PPVr) and interstitial (PIVr) fluid volumes in normal subjects were 7.1 +/- 1.4 and 7.6 +/- 1.3 ml.100 cm-3 lung (mean +/- SD; n = 13) at mid-tidal volume, respectively. In patients with the adult respiratory distress syndrome, PPVr and PIVr were 7.0 +/- 2.9 and 15.9 +/- 4.6 ml.100 cm-3 lung (n = 18), respectively. The pulmonary artery wedge (Paw) pressure was normal (12.5 +/- 2.5 mmHg; n = 5). In patients with pulmonary oedema due to left heart disease, PPVr and PIVr were 7.2 +/- 2.7 and 12.1 +/- 3.7 ml.100 cm-3 lung (n = 8), respectively. The mean Paw pressure in this group was high (28.5 +/- 3.9 mmHg).     

Abnormal ventilatory control in Parkinson's disease--further evidence for non-motor dysfunction

There has been increasing recognition of pre-motor manifestations of Parkinson's disease (PD) resulting from early brainstem involvement. We sought to determine whether ventilatory control is abnormal. Patients with PD without respiratory disease were recruited. Spirometry, lung volumes, diffusing capacity and respiratory muscle strength were assessed. Occlusion pressure and ventilation were measured with increasing CO(2). Arterial blood gases were taken at rest and following 20 min exposure to 15% O(2). A linear correlation assessed associations between respiratory function and indices of PD severity. 19 subjects (17 males) with mild-moderate PD were studied (mean (SD) age 66 (8) years). Respiratory flows and volumes were normal in 16/19. Maximum inspiratory and expiratory pressures were below LLN in 13/19 and 15/19 respectively. 7/15 had a reduced ventilatory response to hypercapnia and 11/15 had an abnormal occlusion pressure. There was no correlation between impairment of ventilatory response and reduction in respiratory muscle strength. Response to mild hypoxia was normal and there were no associations between disease severity and respiratory function. Our findings suggest that patients with mild-moderate PD have abnormal ventilatory control despite normal lung volumes and flows.     

Efficacy of Bronchoscopic Lung Volume Reduction by Endobronchial Valves in Patients with Heterogeneous Emphysema: Report on the First Asian Cases

Although many patients with severe emphysema have benefited from bronchoscopic lung volume reduction (BLVR) worldwide, experience of BLVR in Asian emphysema patients is scarce. Between July 2012 and March 2013, seven patients with advanced heterogeneous emphysema underwent BLVR in the Asan Medical Center. They had severe dyspnea and poor lung function (Modified Medical Research Council dyspnea scale 3-4; median forced expiratory volume in 1 sec [FEV₁], 0.59 L [19.0 % predicted]; median 6-min walk distance [6MWD], 195 m). Endobronchial valves were inserted into the target lobe which was most hyperinflated and least perfused, and had no collateral ventilation with other lobes. Six patients showed clinical improvement after 1 month. Of them, 2 patients improved to dyspnea scale 1 and 4 patients did to scale 2 (P = 0.026). The median FEV₁ increased from 0.59 to 0.89 L (51%; P = 0.028) and the median 6MWD increased from 195 to 252 m (29.2%; P = 0.028). Two patients developed a pneumothorax (one requiring drainage) and one patient experienced slight hemoptysis; however, there were no other serious adverse events. BLVR is effective in Asian advanced emphysema patients, with noted clinical improvements in lung function and exercise capacity.

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The relationship between self-efficacy and self-reported physical functioning in chronic obstructive pulmonary disease and chronic heart failure

In this study, the authors investigated whether self-reported physical functioning of patients with chronic obstructive pulmonary disease (COPD) and chronic systolic heart failure (CHF) was primarily explained by illness-specific differences related to diagnosis or whether more generic factors also contributed to their physical functioning. Consecutive patients with COPD (n = 56; mean age = 67.8, SD = 8.5) and CHF (n = 65; mean age = 60.0, SD = 10.2)from the outpatient clinics of a university hospital and a general hospital completed a self-report questionnaire, including the Rand-36 Health Survey, Cantril's ladder, the Mastery scale, the Perceived Health Competence Scale, and the Self-efficacy scale. COPD patients scored significantly worse in self-reported physical and psychological functioning and perceived health competence than did patients with CHF Regression analysis revealed that both the diagnosis and the illness severity contributed to self-reported physical functioning, although self-efficacy explained the main part of physical functioning. Therefore, important aims in the treatment of patients with COPD and CHF should be not only improving physical functioning but also enhancing self-efficacy.     

Does the oxidative stress in chronic obstructive pulmonary disease cause thioredoxin/peroxiredoxin oxidation?

The thioredoxin/peroxiredoxin system comprises a redox-regulated antioxidant family in human lung; its significance, regulation, or oxidation has not been evaluated in smoking-related lung diseases. Here, we present the expression of the thioredoxin/peroxiredoxin system in lung biopsies from normal lung (n = 14), smokers (n = 21), and patients with chronic obstructive pulmonary disease (COPD, n = 38), and assess the possible inactivation/oxidation of this system by nonreducing Western blotting, two-dimensional gel electrophoresis, and mass spectrometry. Our study shows that the thiol status of the Trx/Prx-system can be modulated in vitro, but it appears to have high resistance against the oxidative stress in COPD.     

Swyer-James (MacLeod) syndrome with placental transmogrification of the lung: a case report and review of the literature

Swyer-James (MacLeod) syndrome is an acquired form of unilateral hyperlucency of the lung and is characterized by the development of severe emphysema, bronchiectasis, and/or bronchiolitis obliterans. It may develop as a complication of repeated episodes of pulmonary infection resulting in bronchiolitis obliterans and obstruction of small airways. Most patients with Swyer-James (MacLeod) syndrome can be managed clinically, and the pathologic features of the syndrome have been described in only a few reports. Placental transmogrification of the lung is a rare histopathologic finding that has been described in patients with severe emphysema associated with cigarette smoking, congenital bullous emphysema, and fibrochondromatous hamartomas of the lung and is characterized by the development of peculiar structures in the pulmonary parenchyma that resemble placental villi. To our knowledge, placental transmogrification of the lung has not been previously described in patients with Swyer-James (MacLeod) syndrome. We encountered a 32-year-old man with a history of childhood asthma who presented with progressively severe exertional dyspnea and had unilateral right lung hyperlucency. The patient underwent a right pneumonectomy. Examination of the lung revealed severe mixed centriacinar-panacinar emphysema in all lobes, bullous emphysema in the upper lobe, bronchiectases, mild interstitial pneumonia with fibrosis, and placental transmogrification of the pulmonary parenchyma of all 3 lobes. Here, we review the pathology of Swyer-James (MacLeod) syndrome and the possible pathogenesis of villous-like changes in the lung tissues.     

The relationship between sleep quality and dyspnoea severity in patients with COPD

ObjectivesThis study aimed to determine sleep quality, frequency and severity of dyspnoea in COPD patients and to evaluate the relationship between dyspnoea severity and sleep quality.MethodThe sample of the study consisted of 110 patients admitted to the Chest Diseases polyclinic of a private hospital and diagnosed as COPD for at least one year. The data of the study were collected using the “Individual Information Form”, “COPD and Asthma Sleep Scale (CASIS)” and “Medical Research Council (MRC) Dyspnoea Scale”.ResultsIt was found that 6.4% of the patients did not experience dyspnoea, 34.5% had mild, 40.9% had moderate, and 18.2% had severe dyspnoea. The mean CASIS score of the patients without dyspnoea was 29.08±7.83, with mild dyspnoea was 40.22±9.30, with moderate dyspnoea was 50.31±8.97 and with severe dyspnoea was 56.96±13.13. There was a statistically significant difference between dyspnoea severity and mean CASIS score (p=0.001). Correlation analysis between MRC dyspnoea scale and CASIS score showed a significant positive correlation (r=0.61 p=0.001).ConclusionIt was concluded that the majority of COPD patients had moderate or poor sleep quality and dyspnoea. As dyspnoea severity increases, sleep quality decreases.     

Redistribution of pulmonary blood flow in interstitial lung diseases: the chest radiograph as a physiologic tool

Posteroanterior radiographs of the chest showed enlargement of vessels in the upper lung fields in 18 of 29 patients with interstitial lung diseases, despite normal pulmonary wedge pressures and normal or reduced pulmonary blood volumes. The degree of such redistribution ("diversion") did not correlate either with the severity of pulmonary hypertension observed at cardiac catheterization or with radiologic assessment of predominance of disease at the lung bases. Diversion did correlate with several indices of disease severity: reduction in vital capacity, reduction in diffusing capacity, reduction in pulmonary blood volume and radiographic severity of parenchymal abnormalities. Furthermore, diversion correlated with lung height, a variable which was not statistically related to the other indices of disease severity. Distension of upper lung vessels occurs in interstitial lung diseases as the result of a decreased hydrostatic gradient over which the lung is perfused (decreased lung height), partial obliteration of the vascular bed (decreased pulmonary volume), and, more speculatively, decreased extravascular pressure (increased lung recoil).     

Lung volumes and diffusion capacity in sickle cell trait

Patients with sickle cell anemia have a restrictive ventilatory pattern, with reduction in diffusion capacity of the lung (DLco) and lung volumes. Diffusion capacity and lung volumes are reported as either normal or reduced in subjects with sickle cell trait. Thirteen subjects with sickle cell trait, age range 25 to 79 years, were compared with 13 normal subjects matched for age, sex, height, and smoking patterns. There was no significant difference in mean values of DLco or lung volume for the two groups. Neither was there a consistent difference for age-matched individuals. Normal lung function in sickle cell trait as opposed to sickle cell disease is probably related to the fact that the former have fewer, if any, pulmonary infectious and infarctive episodes.     

Chitotriosidase in the Pathogenesis of Inflammation,Interstitial Lung Diseases and COPD

As a member of 18 glycosyl hydrolase (GH) family, chitotriosidase (Chitinase 1, CHIT1) is a true chitinase mainly expressed in the differentiated and polarized macrophages. CHIT1 is an innate immune mediator that digests the cell walls of chitin-containing eukaryotic pathogens, such as fungi. However, CHIT1 is dysregulated in granulomatous and fibrotic interstitial lung diseases characterized by inflammation and tissue remodeling. These include tuberclosis, sarcoidosis, idiopathic pulmonary fibrosis, scleroderma-associated interstitial lung diseases (SSc-ILD), and chronic obstructive lung diseases (COPD). CHIT1 serum concentration correlates with the progression or the severity of these diseases, suggesting a potential use of CHIT1 as a biomarker or a therapeutic target. Recent studies with genetically modified mice demonstrate that CHIT1 enhances TGF-β1 receptor expression and signaling, suggesting a role in initiating or amplifying the response to organ injury and repair. This additional CHIT1 activity is independent of its enzymatic activity. These studies suggest that CHIT1 serves a bridging function; it is both an innate immune mediator and a regulator of tissue remodeling. This review will focus on recent data linking CHIT1 to the pathogenesis of inflammation, interstitial lung disease, and COPD.