Activation of the Prefrontal Cortex Is Associated with Exertional Dyspnea in Chronic Obstructive Pulmonary Disease
Yuji HigashimotoNoritsugu HondaToshiyuki YamagataToshiki MatsuokaKazushige MaedaRhyuji SatohOsamu NishiyamaHiroyuki SanoTakashi IwanagaTakayuki MiyaraMasato MurakiKatsuyuki TomitaHiroaki KumeIchiro MiyaiYuji TohdaKanji Fukuda
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Exertional dyspnea is the primary symptom that limits exercise in patients with chronic obstructive pulmonary disease (COPD). It is unknown which activated brain area is associated with this symptom in COPD patients.To investigate the activation of cortical areas associated with dyspnea during exercise in COPD patients.COPD patients (n = 10) and age-matched controls (n = 10) performed mild-intensity constant work rate cycle exercise (40% of their symptom-limited peak work rates) for 10 min, while cerebral hemodynamics and oxygenation were measured by near-infrared spectroscopy (NIRS). Ventilatory responses (breathing pattern and pulmonary gas exchange) and Borg scale ratings of dyspnea and leg fatigue were measured during exercise. Three NIRS probes were placed over the prefrontal and temporoparietal cortical regions of the subjects' heads. Changes in cortical oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total Hb) concentrations from baseline recordings were measured. Increased oxy-Hb (oxygenation) was assumed to reflect cortical activation.Oxy-Hb concentration was significantly increased in the prefrontal region during exercise in both groups but not in the temporoparietal regions. The change in prefrontal oxy-Hb concentration of COPD patients was not different from that of controls. Dyspnea scores were positively correlated with changes in oxy-Hb concentrations of the prefrontal regions in both groups. Multivariate analysis showed that oxy-Hb concentration in the prefrontal region was the best predictor of dyspnea in both groups.Exertional dyspnea was related to activation (oxygenation) of the prefrontal cortex in COPD patients and control subjects.Keywords:
Incremental exercise
现在，医药社区应该很好知道长期的妨碍的肺的疾病(COPD ) 的重要性，有高病态和死亡的一个逐渐地普通的条件。在现代条款， COPD 来了意味着并发的长期的支气管炎，气喘的支气管炎和肺气肿。香烟吸烟长作为占优势的病因论的代理人被认出了。动脉的 hypoxaemia， COPD 的经常的复杂并发症，能导致肺的高血压和英国管 pulmonale。COPD 影响超过 5% 成年人口并且是其病态和死亡在几个国家正在增加的死亡的唯一的主要原因。在中国，确定是困难的多少人与 COPD 被影响。然而，最近的流行病学的调查显示那 COPD 流行在中国是 8.2% 。在男人的 COPD 流行比在女人显著地高(12.4% cf 5.1%) 。在农村区域的流行在城市的区域(8.8%cf7.8%) 比那高。有 COPD 的病人， 61.5% 是吸烟者。报告也声明 COPD 是在在中国和在城市的区域的死亡的第四个领先的原因的农村区域的死亡的主要原因，升起到在 2020 的死亡的第三个领先的原因。疾病的流行与年龄增加，最高的率在超过 70 年岁的人看。COPD 是有升起的发生和世界范围的流行的死亡的唯一的主要原因，显示它一逐渐地使人烦恼的。
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The aim of the present study was to determine whether the oxygenation level in an inactive muscle during an incremental exercise test, determined by near-infrared spectroscopy, influences the maximal oxygen uptake (Vo2max). The oxygenation level at the onset of incremental exercise was higher than that at rest and started to decrease at a high power output. A minimal level was observed at exhaustion during incremental exercise. Vo2 increased linearly after some delay, and the rate of increase in Vo2 was greater at a higher power output. Heart rate increased linearly after the time delay, and the rate of increase in heart rate did not change. There was a significant correlation between Vo2max and oxygenation level in inactive muscle at exhaustion (r = -0.89). We therefore concluded that the oxygenation level in inactive muscle at exhaustion during incremental exercise is associated with an individual difference in Vo2max.
Incremental exercise
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목적: COPD 환자에서 우심실비대와 기능장애는 흔한 반면, 좌심실의 수축기능은 비교적 잘 보존되는 것으로 알려져 있다. 최근에 COPD 환자에서 좌심실이완기능장애가 흔하다는 보고가 있다. 저자들은 심장초음파를 이용하여 COPD 환자에서의 심장의 구조와 기능의 변화를 평가해 보고자 하였다. 방법: 심장질환을 진단받은 적이 없는 안정상태의 COPD 환자 69명과 정상폐활량을 가진 대조군 22명에서 심장초음파검사 결과를 비교하였고, Global initiative for chronic Obstructive Lung Disease (GOLD) 기준에 따른 COPD의 중증도에 따라 심장의 구조와 기능에 변화가 있는지 평가하였다. 결과: COPD 환자가 대조군보다 몸무게가 유의하게 작았고(p=0.001), 흡연량이 많았다(p=0.002). 심장초음파검사결과 COPD 환자의 좌심실이완기말지름(p<0.001), 좌심실수축기말지름(p=0.020), 좌심방지름(p=0.026)과 좌심실질량이 대조군보다 유의하게 작았다(p=0.003). 그러나 좌심실의 이완기능을 나타내는 여러 지표와 평균 우심실수축기압은 COPD 환자와 대조군 사이에 차이가 없었다. COPD의 중증도에 따라 몸무게(p<0.001), 체질량지수(p<0.001)와 좌심실질량이 유의한 차이를 보였고(p=0.011), 좌심실질량과(r=0.432)(p<0.001) 체질량지수는 FEV1% 예측치와 유의한 양의 상관관계를 보였다(r=0.600)(p<0.001). 결론: COPD 환자와 대조군 사이에 심박출계수는 차이가 없음에도 불구하고, COPD 환자에서 좌심실질량, 좌심방지름, 좌심실이완기말지름, 좌심실수축기말지름은 대조군보다 유의하게 작았다. 특히, 좌심실질량은 폐기능이 감소할수록 감소하였다.
Obstructive lung disease
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The purpose of this study was to observe the changes in skeletal muscle ogygenation at different incremental exercise on bicycle ergometer and to analyze the production mechanism of oxygenation and anaerobic threshold turing points and its effects in evaluating maximal aerobic capacity(MAC).17 participants were divided into two groups(Group A and Group B) according to their athletic career.Incremental exercise was performed on cycle egometer and respired gas was continuously sampled by IMA for breath-by-breath determination of VE,VCO2 and VO2.Blood sample was taken from fingertip for analyzing blood lactate concentration.Moreover,muscle oxygenation from quadricepts muscle was measured simultaneously.The result indicated that at the beginning of exercise,muscle oxygenation immediately declined with greade increase and kept balance gradually when the same grade exercise continued.As the workload was upgraded,the muscle oxygenation sharply declined correspondent to the intensity of the exercise.The change of muscle oxygenation during incremental exercise was correlated with Bla and VO2.It could be concluded that NIRS was a fairly sensitive method for measuring muscle oxygenation during exercise.The turning point of muscle oxygenation which was correspondent with the breaking points of Bla,VT and HR might indicate that NIRS could be effectively utilized for determining MAC.
Incremental exercise
Cycle ergometer
Aerobic capacity
Lactate threshold
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Patients with chronic heart failure (HF) have a reduced skeletal muscle blood flow which can in part explain reduced exercise tolerance and increased ventilation. All the techniques commonly employed to measure skeletal muscle blood flow have limitations that reduce their accuracy and clinical application. Near infrared spectroscopy (NIRS) is a noninvasive, inexpensive, and reproducible technique able to monitor muscle oxygenation both at rest and during exercise, providing information about tissue perfusion. The principle of NIRS is based on the observation that the light absorption characteristics of hemoglobin (Hb) and myoglobin (Mb) in the near infrared region (700-1000 nm) change depending on their relative saturations. In humans, NIRS has been employed to monitor skeletal muscle oxygenation during exercise and/or after cuff-induced limb ischemia in normal subjects as well as patients with chronic HF. Patients with chronic HF have a reduced Hb/Mb oxygenation at any matched work rate and a more rapid deoxygenation above the anaerobic threshold than normal subjects. More recently, NIRS has been used to determine the kinetics of muscle oxygenation in recovery after constant work rate exercise, providing evidence of an inverse relation with cardiac function as assessed by peak oxygen uptake. In conclusion, NIRS appears to be a new promising noninvasive technique for studying muscle oxygenation in a variety of experimental models. (c)1999 by CHF, Inc.
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瞄准：为了调查手术后的肺的复杂并发症(POPC ) 的各种各样的类型的发生并且评估起作用的仙子的意义，在有食道的癌症的病人的动脉的血气体在食管切除术以后与长期的妨碍的肺的疾病(COPD ) 伴随了。方法：358 个病人被划分成 POPC 组和 COPD 组。我们为食道的癌症在食管切除术以后执行了 358 个连续病人的回顾的评论与或没有 COPD 在手术后的肺的复杂并发症上估计 COPD 的可能的影响。我们在 1 s (FEV1 ) 根据预言百分比的强迫的吐气的体积分类 COPD 进四个等级并且在四个等级之中分析了复杂并发症的发生率。Perioperative 动脉的血气体在 COPD 组并且与 POPC 组相比在病人被测试与或没有肺的复杂并发症。结果：有 COPD 的病人(29/86， 33.7%) 没有 COPD，比那些有更肺的复杂并发症(36/272， 13.2%)(P 或 =80% 预言) COPD (P < 0.05 ) 。PaO (2 ) 被减少， PaCO (2 ) 在第一个手术后的星期内在 COPD 组与肺的复杂并发症在病人被增加。结论：COPD 的标准是为在经历食管切除术的食道的癌症病人的肺的复杂并发症的批评预言者。COPD 的严厉影响肺的复杂并发症的发生率，并且预言百分比的 FEV1 是为在有 COPD 的病人的肺的复杂并发症的一个好预兆的变量。动脉的血气体在指导起作用的仙子是有用的管理。
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서론: 만성폐쇄성폐질환(chronic obstructive pulmonary disease, COPD)는 최근 사망률과 유병률이 증가하는 만성적인 질환이다. 국내에서의 유병률은 간헐적으로 보고되고 있지만, 수년간에 걸친 COPD 유병률의 변화와 그리고 COPD 위험인자의 변화에 관한 연구는 없었다. 이 연구는 국민건강영양조사 자료를 이용하여 8년 간의 COPD 빈도와 위험인자의 변화에 관해 알아보고자 하였다. 방법: 2007년부터 2014년 간의 국민건강영양조사 원시자료를 이용하였으며, 이중 나이 40세 이상이면서 폐기능 검사를 시행한 총 24,500명 (남자 43.8%, 여자 56.2%)의 자료를 분석하였다. COPD의 진단은 FEV1/FVC 비가 0.7 미만인 경우로 하였다. COPD 위험인자의 분석에는 거주 지역, 소득, 교육, 흡연, BMI, vitamin D를 이용하였다. 결과: COPD 빈도는 2007년도에 18.4%로 가장 높았으며, 이후 감소하는 추세를 보여 2009년에는 11.9% 였다. 2011년도부터 다시 증가하기 시작하여 2014년도 까지 COPD 빈도는 13.5%에서 15.4 % 였다. 여자와 남자 모두 비슷한 형태를 보였다. 다항 로지스틱 회귀 분석에서 2007년도부터 2014년 전체를 대상으로 하였을 때, COPD 위험인자는 저소득, 낮은 교육, 흡연, 낮은 BMI 와 혈중 vitamin D 였으며, 거주 지역은 위험인자가 아니었다. 년도별 분석에서도 저소득, 흡연, 낮은 BMI는 COPD의 위험인자였지만, 낮은 교육은 2009년도 이후부터는 COPD의 위험인자가 아니었다. Vitamin D는 년도에 따라 다른 결과를 보였다. 결론: 낮은 교육 수준은 COPD의 위험인자가 아니었다.
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PURPOSE: To determine if fatigue at maximal aerobic power output was associated with a critical level of cerebral oxygenation, thirteen male cyclists performed incremental exercise tests (25 W·min−1 ramp) under normoxic (NORM: 21% FIO2) and acute hypoxic (HYPOX: 12% FIO2) conditions. METHODS: Near infrared spectroscopy (NIRS) was used to assess changes in cerebral and muscle oxygenation during incremental exercise. Concentration (μM) changes in oxy- and deoxy-hemoglobin (ΔO2Hb, Δ HHb) in the left vastus lateralis and frontal cortex (Oxymon, Artinis, The Netherlands) were measured and used to calculate an index of change in tissue oxygenation (ΔHbdiff = ΔO2Hb - ΔHHb). Repeated measures ANOVA analyses were performed across treatments and relative workrates (α = 0.05). RESULTS: During NORM, cerebral oxygenation (ΔHbdiff) was maintained up to 75% peak power output (Powerpeak), but decreased thereafter. Muscle oxygenation (ΔHbdiff) progressively decreased up to 75% Powerpeak, but was unchanged thereafter. During HYPOX cerebral oxygenation progressively decreased across all workrates, while muscle oxygenation again decreased up to 75% Powerpeak and remained unchanged thereafter. The magnitudes of changes were greater in HYPOX than NORM for cerebral but not muscle ΔHbdiff at 100% Powerpeak. CONCLUSION: These results demonstrate a large tolerance for changes in cerebral oxygenation at maximal aerobic power output and do not support the notion that a critical level of frontal cortex oxygenation limits exercise in NORM.Figure
Hypoxia
Vastus lateralis muscle
Incremental exercise
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・GOLD (Global Initiative for Chronic Obstructive Lung Disease) は, EBM (evidence based medi-cine) に基づいて作成され, 2001年に公表されたCOPD (Chronic Obstructive Pulmonary Dis-ease) の治療と管理に関する国際的ガイドラインである。・COPDに関して, 定義, 危険因子, 診断, 管理計画, 薬物治療, 患者教育, 急性増悪の7つのキーポイントを指摘している。・従来の慢性気管支炎や肺気腫などの診断名は用いず, COPDという診断名で新しい定義を規定している。・COPD発症のもっとも重要な危険因子は喫煙である。・COPDの診断にスパイロメトリーが必須である。・COPDの病期分類は, 一秒量 (FEV1) の程度にしたがって重症度を軽症-最重症の4段階に分類しているが, 新たに呼吸機能は正常であるが呼吸器症状 (咳, 痰) がある群をstage 0として設定し, 早期診断と早期予防を重視している。・COPDの管理として, 疾患の評価とモニタリング, 危険因子の縮小, 安定期COPDの管理, 急性増悪の管理の4つの要素を指摘している.・治療は, 全ての病期で, 危険因子の回避 (特に禁煙) とインフルエンザワクチンの接種を推奨している。・薬物治療と非薬物治療に関して, EBMに基づいて段階的治療を推奨している。
Obstructive lung disease
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Introduction: A myriad of factors underlie pacing-/exhaustion-decisions that are made during whole-body endurance performance. The prefrontal cortex (PFC) is a brain region that is crucial for decision-making, planning, and attention. PFC oxygenation seems to be a mediating factor of performance decisions during endurance performance. Nowadays, there is no general overview summarizing the current knowledge on how PFC oxygenation evolves during whole-body endurance performance and whether this is a determining factor. Methods: Three electronic databases were searched for studies related to the assessment of PFC oxygenation, through near-IR spectroscopy (NIRS), during endurance exercise. To express PFC oxygenation, oxygenated (HbO 2 ) and deoxygenated hemoglobin (HHb) concentrations were the primary outcome measures. Results: Twenty-eight articles were included. Ten articles focused on assessing prefrontal oxygenation through a maximal incremental test (MIT) and 18 focused on using endurance tasks at workloads ranging from low intensity to supramaximal intensity. In four MIT studies measuring HbO 2 , an increase of HbO 2 was noticed at the respiratory compensation point (RCP), after which it decreased. HbO 2 reached a steady state in the four studies and increased in one study until exhaustion. All studies found a decrease or steady state in HHb from the start until RCP and an increase to exhaustion. In regard to (non-incremental) endurance tasks, a general increase in PFC oxygenation was found while achieving a steady state at vigorous intensities. PCF deoxygenation was evident for near-to-maximal intensities at which an increase in oxygenation and the maintenance of a steady state could not be retained. Discussion/Conclusion : MIT studies show the presence of a cerebral oxygenation threshold (ThCox) at RCP. PFC oxygenation increases until the RCP threshold, thereafter, a steady state is reached and HbO 2 declines. This study shows that the results obtained from MIT are transferable to non-incremental endurance exercise. HbO 2 increases during low-intensity and moderate-intensity until vigorous-intensity exercise, and it reaches a steady state in vigorous-intensity exercise. Furthermore, ThCox can be found between vigorous and near-maximal intensities. During endurance exercise at near-maximal intensities, PFC oxygenation increases until the value exceeding this threshold, resulting in a decrease in PFC oxygenation. Future research should aim at maintaining and improving PFC oxygenation to help in improving endurance performance and to examine whether PFC oxygenation has a role in other performance-limiting factors.
Respiratory compensation
Incremental exercise
Deoxygenated Hemoglobin
Functional near-infrared spectroscopy
Endurance Training
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