[Cognitive function in patients with chronic obstructive pulmonary disease].

It is increasingly recognized that COPD is a multi-component disease, but little attention has been paid to its effects on cognition. Cognitive dysfunction is associated with increased disability of daily living and mortality. However, it remains to be elucidated in COPD. Our main findings are: 1) cognitive dysfunction in patients with COPD is related to the grade of activity of daily livings and hypoxemia, especially in exercise-induced hypoxemia; 2) cognitive impairment such as perception, attention and short memory are impaired; 3) attention function determined by Trail Making Test is improved by O2 inhalation with the increase in the prefrontal cortex oxygenation; 4) by 8 week exercise training, cognitive function in COPD is improved with the increase in the prefrontal circulation.

Epistatic effects of multiple receptor genes on pathophysiology of asthma - its limits and potential for clinical application.

To date, genome-wide association studies (GWAS) permit a comprehensive scan of the genome in an unbiased manner, with high sensitivity, and thereby have the potential to identify candidate genes for the prevalence or development of multifactorial diseases such as bronchial asthma. However, most studies have only managed to explain a small additional percentage of hereditability estimates, and often fail to show consistent results among studies despite large sample sizes. Epistasis is defined as the interaction between multiple different genes affecting phenotypes. By applying epistatic analysis to clinical genetic research, we can analyze interactions among more than 2 molecules (genes) considering the whole system of the human body, illuminating dynamic molecular mechanisms. An increasing number of genetic studies have investigated epistatic effects on the risk for development of asthma. The present review highlights a concept of epistasis to overcome traditional genetic studies in humans and provides an update of evidence on epistatic effects on asthma. Furthermore, we review concerns regarding recent trends in epistatic analyses from the perspective of clinical physicians. These concerns include biological plausibility of genes identified by computational statistics, and definition of the diagnostic label of 'physician-diagnosed asthma'. In terms of these issues, further application of epistatic analysis will prompt identification of susceptibility of diseases and lead to the development of a new generation of pharmacological strategies to treat asthma.

Neural regulatory mechanism of desire for food: revealed by magnetoencephalography.

Currently, little is known about the brain function that allows individuals to suppress eating behavior. The present study used magnetoencephalography (MEG) to examine changes in neural activity over time that were related to suppression of motivation to eat in 11 healthy males. The MEG experiment consisted of four motivation sessions and four suppression sessions in an alternating and counterbalanced order. During MEG recordings, participants viewed a set of food pictures and mosaic pictures projected onto a screen, and were then asked to rate their motivation to eat and the suppression of the motivation to eat during the recordings. The present study demonstrated a higher ß-band (13-25 Hz) event-related synchronization (ERS) level during the suppression sessions relative to the motivation sessions in the left supplementary motor area (SMA) 200-300 ms after the start of food picture presentation. Similar differences were also observed in θ-band (4-8 Hz) event-related desynchronization (ERD) in the left dorsolateral prefrontal cortex (DLPFC) after 500-600 ms. Negative relationships were observed between these levels of MEG responses and the number of food items for which the participants reported the motivation to eat during the MEG recordings. These findings indicate that the left DLPFC and SMA, particularly the DLPFC, play prominent roles in the suppression of motivation to eat. This may help to clarify the temporal aspects of the neural basis of self-control of appetitive motivation as well as aid development of self-control strategies such as cognitive behavioral therapy for patients with disordered appetite.

Effects of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women.

The purpose of this study was to investigate the effects of 12 weeks of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women. Twenty healthy middle-aged women were recruited for this study. Several measurements were performed pre and post exercise training, including: body weight and composition, peak oxygen consumption (peak VO2), energy intake after the single bout of exercise, and the release of gut hormones with fasting and after the single bout of exercise. Exercise training resulted in significant increases in acylated ghrelin fasting levels (from 126.6 ± 5.6 to 135.9 ± 5.4 pmol/l, P < 0.01), with no significant changes in GLP-1 (from 0.54 ± 0.04 to 0.55 ± 0.03 pmol/ml) and PYY (from 1.20 ± 0.07 to 1.23 ± 0.06 pmol/ml) fasting levels. GLP-1 levels post exercise training after the single bout of exercise were significantly higher than those pre exercise training (areas under the curve (AUC); from 238.4 ± 65.2 to 286.5 ± 51.2 pmol/ml x 120 min, P < 0.001). There was a tendency for higher AUC for the time courses of PYY post exercise training than for those pre exercise training (AUC; from 519.5 ± 135.5 to 551.4 ± 128.7 pmol/ml x 120 min, P = 0.06). Changes in (delta) GLP-1 AUC were significantly correlated with decreases in body weight (r = -0.743, P < 0.001), body mass index (r = -0.732, P < 0.001), percent body fat (r = -0.731, P < 0.001), and energy intake after a single bout exercise (r = -0.649, P < 0.01) and increases in peak VO2 (r = 0.558, P < 0.05). These results suggest that the ability of exercise training to create a negative energy balance relies not only directly on its impact on energy expenditure, but also indirectly on its potential to modulate energy intake.

Changes in salivary antimicrobial peptides, immunoglobulin A and cortisol after prolonged strenuous exercise.

The aim of the present study was to examine whether amount of oral antimicrobial components, human ß-defensin-2 (HBD-2), cathelicidin (LL-37), and immunoglobulin A (IgA), might be affected by prolonged strenuous exercise. Ten young male volunteers either exercised on recumbent ergometer at 75% [Formula: see text] for 60 min (exercise session) or sat quietly (resting session). Saliva samples were obtained at 60-min intervals during sessions for measurements of saliva antimicrobial components (HBD-2, LL-37, and IgA), saliva cortisol and osmolality. Saliva flow rate was decreased and saliva osmolality was increased during the 60-min exercise. Saliva HBD-2 and LL-37 concentrations and secretion rates were increased during and after the exercise, whereas saliva IgA concentration and secretion rates were decreased after the exercise. Saliva cortisol was increased during and after the exercise. The areas under the curve of the time courses of saliva levels of HBD-2 and LL-37 were negatively correlated with those of cortisol levels in saliva. The present findings suggested that a single bout of prolonged strenuous exercise caused a transient increase in the oral HBD-2 and LL-37 levels.

Gene polymorphism of epidermal growth factor receptor and airway hyperresponsiveness in young allergic subjects without respiratory symptoms.

BACKGROUND: Airway hyperresponsiveness (AHR) in young asymptomatic adults with atopy can be one of indicators of future symptomatic asthma. We aimed to investigate genetic association of epidermal growth factor receptor (EGFR) with the asymptomatic AHR. MATERIAL/METHODS: We recruited one-hundred and eighty-nine allergic volunteers (mean age 19.5+/-1.4 y.o.) without history of respiratory symptoms, measured bronchial responsiveness to methacholine (0.3 to 10.0 mg/ml) and classified them into subjects with AHR and those without AHR according to a cutoff level of PC20 (8.0 mg/ml). Then, we genotyped 12 SNPs on EGFR gene, and estimate total imbalance of haplotypes frequencies within haplotype block between two groups. RESULTS: Seventy-two (38.1%) in 189 subjects exhibited 20% decrease in FEV1 from the baseline values by inhalation of methacholine 8.0mg/ml or less. Significant results were observed in the following haplotype block: rs 4947972 - rs 12718945 - rs 2072454 (block-1), rs 4947972 - rs 12718945 - rs 2227983 (block-2), or rs 4947972 - rs 12718945 - rs 2293347 (block-3). In each haplotype block, higher frequency of a haplotype, C-T-C (block-1), C-T-A (block-2) and C-T-A (block-3), was observed in subjects with AHR than in those without AHR (odds ratio and the corresponding P value; 3.289 and 0.00087 (block-1), 3.436 and 0.00055 (block-2), and 4.036 and 0.00181 (block-3), respectively). No significant differences were observed in serological parameters and pulmonary function between two subject groups. CONCLUSIONS: Our results indicate that the EGFR gene polymorphism might be associated with presence of asymptomatic AHR in young allergic adults.

Effects of aquatic exercise training using water-resistance equipment in elderly.

To prevent falls in Japan, both gait and resistance training of the lower extremities are recommended. However, resistance training for the elderly induces muscle damage. Recently, aquatic exercise using water buoyancy and resistance have commonly been performed by the elderly. We have now produced new water-resistance equipment. The purpose of the present study was to evaluate the efficacy of aquatic exercise training using the new equipment for the elderly. Subjects were divided into two groups: a resistance group of 12 subjects (using water-resistance equipment) and a non-resistance group of eight subjects (without the equipment). The aquatic exercise training was 90 min, three times per week for 8 weeks, and mostly consisted of walking. All subjects underwent anthropometric measurements, physical performance testing, and profile of mood states (POMS). Significant improvements were observed in muscle strength in plantar flexion, and the timed up and go test (TUG) in both groups. Additionally, 10-m obstacle walking and 5-m maximum walking speed and length with eye-open were significantly improved in the resistance group. Also, a low negative correlation was found between the degree of change in TUG and POMS (tension and anxiety) scores in the resistance group. As it became easier to maintain posture, stand, and move, tension and anxiety in everyday life were alleviated with improvement of strength of the lower extremities and balance function. The present aquatic exercise training using water-resistance equipment may be used by the elderly to improve balance and walking ability, which are associated with the prevention of falls.

Comparable effects of moderate intensity exercise on changes in anorectic gut hormone levels and energy intake to high intensity exercise.

There is growing interest in the effects of exercise on plasma gut hormone levels and subsequent energy intake (EI) but the effects of mode and exercise intensity on anorectic hormone profiles on subsequent EI remain to be elucidated. We aimed to investigate whether circulating peptide YY(3-36) (PYY(3-36)) and glucagon-like peptide-1 (GLP-1 or GCG as listed in the HUGO Database) levels depend on exercise intensity, which could affect subsequent EI. Ten young male subjects (mean+/-s.d., age: 23.4+/-4.3 years, body mass index: 22.5+/-1.0 kg/m(2), and maximum oxygen uptake (VO(2 max)): 45.9+/-8.5 ml/kg per min) received a standardized breakfast, which was followed by constant cycling exercise at 75% VO(2 max) (high intensity session), 50% VO(2 max) (moderate intensity session), or rest (resting session) for 30 min. At lunch, a test meal was presented, and EI was calculated. Blood samples were obtained during three sessions for measurements of glucose, insulin, PYY(3-36), and GLP-1, which includes GLP-1 (7-36) amide and GLP-1 (9-36) amide. Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions. Of note, increase in area under the curve values for GLP-1 levels was negatively correlated with decrease in the EI in each exercise session (high: P<0.001, moderate: P=0.002). The present findings raise the possibility that each gut hormone exhibits its specific blood kinetics in response to two different intensities of exercise stimuli and might play differential roles in regulation of EI after exercise.

Decrease in serum levels of advanced glycation end-products by short-term lifestyle modification in non-diabetic middle-aged females.

BACKGROUND: Advanced glycation end products (AGEs) play an important role in development of atherosclerosis in diabetes and uremic diseases. However, there is currently little information available on the effects of lifestyle modification on circulating AGEs in subjects without these diseases. MATERIAL/METHODS: Serum levels of Nepsilon-(carboxymethyl) lysine (CML), pentosidine, derivatives of reactive oxygen metabolites (d-ROMs), adipokines, and renal function were determined in forty-seven middle-aged females. Among them, seventeen participated in a 12-week lifestyle modification (LM) program and twelve age-matched subjects were assigned to a control group. The LM program consisted of an initial educational session and encouragement. RESULTS: At baseline, serum HDL-cholesterol was correlated with CML level (P=0.003), whereas body fat mass (P=0.012) and fat consumption (P=0.007) were correlated with pentosidine levels. After intervention, significant reductions were observed in the LM group in body fat, serum HDL-cholesterol, CML, and pentosidine. Of note, in the LM group, average number of steps in daily walking was significantly correlated with decrease in CML level (P=0.044). Decrease in pentosidine level exhibited significant positive correlations with reduction in body weight (P=0.007) and body fat mass (P=0.038). CONCLUSIONS: The present findings suggest lifestyle modification as a promising approach to reducing circulating AGE levels even in healthy middle-aged females with neither overt diabetes nor renal dysfunction.

Changes in gut hormone levels and negative energy balance during aerobic exercise in obese young males.

We examined whether changes in gut hormone levels due to a single bout of aerobic exercise differ between obese young males and normal controls, and attempted to determine the involvement of hormonal changes during exercise in the regulation of energy balance (EB) in these obese subjects. Seven obese and seven age-matched subjects of normal weight participated in exercise and rest sessions. Subjects consumed a standardized breakfast that was followed by constant cycling exercise at 50% VO(2max) or rest for 60 min. At lunch, a test meal was presented, and energy intake (EI) and relative energy intake (REI) were calculated. Blood samples were obtained at 30 min intervals during both sessions for measurement of glucose, insulin, glucagon, ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise. The areas under the curve (AUC) of the time courses of PYY and GLP-1 levels did not significantly differ between the two groups. In contrast, EI and REI were decreased by exercise in both groups, and energy deficit was significantly larger in obese subjects than in normal controls. The present findings suggest that short-term EB during a single exercise session might be regulated not by increased amounts of these gut hormones per se.

Association of beta2-adrenoreceptor genotypes with bronchodilatory effect of tiotropium in COPD.

BACKGROUND AND OBJECTIVE: Recently, there has been interest in interactions of beta(2) adrenergic receptors (beta(2)-AR) and muscarinic acetylcholine receptors (mAChR), which share intracellular signal transduction systems. The aim of the present study was to investigate whether bronchodilator response to tiotropium is influenced by beta(2)-AR genotype in patients with COPD who show poor responsiveness to inhaled beta(2)-agonists. METHODS: After a 4-week run-in period, patients with COPD were treated with inhaled tiotropium bromide (18 microg once daily) for 8 weeks. Spirometric measurements and reversibility testing with inhaled beta(2)-AR agonists were performed and health-related quality of life was assessed using the St George's respiratory questionnaire (SGRQ) before and after treatment. Genomic DNA was prepared from peripheral blood and individual genotypes at amino acid 16 of the beta(2)-AR were examined. RESULTS: Forty-four patients with COPD completed the study. COPD patients with the Arg/Arg genotype (n = 22) had a significant increase in FEV(1) during treatment compared with those without the Arg/Arg genotype (n = 22) (FEV(1), P = 0.009; FEV(1)%, P = 0.006). While all component and total scores on the SGRQ improved significantly in both genetic groups, changes in impact and total scores were significantly greater in patients with Arg/Arg compared with those without (total scores, P = 0.005; impact scores, P < 0.001). CONCLUSIONS: These findings indicate that the homozygous Arg/Arg genotype at amino acid 16 of the beta(2)-AR could affect bronchodilator response to tiotropium in patients with COPD with significant effects on health-related quality of life.

Effects of tiotropium or combined therapy with salmeterol on hyperinflation in COPD.

BACKGROUND: Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation. METHODS: Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks. RESULTS: Before treatment, inspiratory capacity (IC) after hyperventilation decreased significantly in a breathing frequency-dependent manner. After tiotropium administration, forced expiratory volume in one second (FEV1) increased significantly. IC after hyperventilation decreased significantly in a breathing frequency-dependent manner; however, IC was significantly greater than that before treatment (at rest, p=0.001; after hyperventilation at twice the resting respiratory rate, p=0.0009; and after hyperventilation at three times the resting respiratory rate, p<0.0001). The SGRQ score also improved significantly. After combined therapy with salmeterol, FEV1 increased significantly compared with after tiotropium alone. However, there was no significant difference between the IC after tiotropium alone and that after combined therapy, at each stage. However, after combined therapy the SGRQ score significantly improved compared with that after tiotropium alone. CONCLUSIONS: Tiotropium improved airflow obstruction and hyperventilation-evoked hyperinflation. In combination with salmeterol, the improvement in airflow obstruction was greater, but hyperventilation-evoked hyperinflation was not further improved.

Induced sputum analysis in asymptomatic young adults with bronchial hyperresponsiveness to methacholine.

BACKGROUND AND OBJECTIVES: BHR is a clinical feature of asthma and factors crucial to the development of BHR remain to be elucidated. Asymptomatic BHR also occurs in the general population. This study examined the prevalence of asymptomatic BHR in a population of young Japanese atopic individuals to identify whether airway inflammation is present in asthmatic patients but not in asymptomatic subjects with BHR. METHODS: Fifty atopic volunteers (aged 18-23 years) without lower respiratory symptoms were recruited and their bronchial responsiveness to methacholine was measured in order to categorize them into two groups, those with BHR (PC(20) below 8 mg/mL) and those without BHR. We evaluated the inflammatory cell profiles and measured IL-5 and IL-13 levels in sputum from subjects of each group by ELISA. Results were compared with those for young adult asthmatic patients. RESULTS: In the young atopic group, 17 subjects (34.0%) exhibited BHR. Compared with asthmatic patients sputum from asymptomatic subjects with BHR contained significantly lower numbers of eosinophils (P < 0.001) and had significantly lower levels of IL-5 (P = 0.088) and IL-13 (P = 0.032). There were no significant differences in each inflammatory parameter between the two asymptomatic groups. CONCLUSIONS: In young adult atopic subjects with asymptomatic BHR, airway inflammation does not necessarily play a determining role in the development of BHR to methacholine itself, though it might be an important factor in the onset of asthma.

Thresholds of physical activities necessary for living a self-supporting life in elderly women.

BACKGROUND: To decide the minimal levels (thresholds) of physical activities necessary for a self-supporting life using discriminate analysis between community-dwelling elderly individuals and daycare-service-receiving elderly individuals in Japan. METHOD: A total of twenty-six elderly women, including twelve living a self-supporting life and fourteen using a daycare service, were recruited in this study. The parameters examined were physical performance, activities of daily living, exercise capacity. Discriminate analysis was used to determine the thresholds of physical activities needed to live a self-supporting life. RESULTS: Muscle masses, grip strength, lower-extremity muscle force, gait ability and balance function in elderly individuals living a self-supporting life were significant higher than those in elderly individuals using a daycare service. A threshold of physical ability over 75% classifies accurately using the methods of discriminate analysis indicate total body muscle mass, thigh muscle mass, knee extension force, 6 min walking distance (6MD), 10 m obstacle walking time, Activity of daily living (ADL) index and daily steps. CONCLUSIONS: The present study indicates that thresholds of physical activities including gait abilities, muscle force, and muscle mass are very important factors in maintaining a self-supporting life for elderly individuals. Thresholds of physical activities were more effective than standard values of physical activity for elderly individuals using a care service in meeting the goals of rehabilitation.

Which common NIRS variable reflects muscle estimated lactate threshold most closely?

Various near-infrared spectroscopy (NIRS) variables have been used to estimate muscle lactate threshold (LT), but no study has determined which common NIRS variable best reflects muscle estimated LT. Establishing the inflection point of 2 regression lines for deoxyhaemoglobin (DeltaHHb(i.p).), oxyhaemoglobin (DeltaO2Hb(i.p.)), and tissue oxygenation index (TOIi.p.), as well as for blood lactate concentration, we then investigated the relationships between NIRS variables and ventilatory threshold (VT), LT, or maximal tissue hemoglobin index (nTHImax) during incremental cycling exercise. DeltaHHb(i.p.) and TOI(i.p.) could be determined for all 15 subjects, but DeltaO2Hb(i.p.) was determined for only 11 subjects. The mean absolute values for the 2 measurable slopes of the 2 continuous linear regression lines exhibited increased changes in 3 NIRS variables. The workload and VO2 at DeltaO2Hb(i.p.) and nTHImax were greater than those at VT, LT, DeltaHHb(i.p.), and TOI(i.p.). For workload and VO2, DeltaHHb(i.p.) was correlated with VT and LT, whereas DeltaO2Hb(i.p.) was correlated with nTHImax, and TOI(i.p.) with VT and nTHImax. These findings indicate that DeltaO2Hb strongly corresponds with local perfusion, and TOI corresponds with both local perfusion and deoxygenation, but that DeltaHHb can exactly determine deoxygenation changes and reflect O2 metabolic dynamics. The finding of strongest correlations between DeltaHHb and VT or LT indicates that DeltaHHb is the best variable for muscle LT estimation.

Effects of electrical stimulation and voluntary exercise on muscle oxygenation assessed by NIRS.

In this study, we investigated the effect of low-frequency ES (electric stimulation) to muscle oxygenation level by NIRS (near infrared spectroscopy) from comparing with V-Ex (voluntary exercise). Ten subjects performed ES and V-Ex test in supine position on a bed with 90 degrees flexion of the right knee joint and fixation of the right ankle to the end of the bed with a strap. NIRS probe was placed on middle point of the vastus lateralis, and four electrodes were placed across the motor point of the rectus femoris and vastus lateralis. Stimulation voltage was started at 20 V (20 Hz, pulse duration: 200 micros, duty-cycle: 1s-1s), and then was increased at a rate of 3 V/30 s until maximal tolerance level. V-Ex (isometric knee extension) was performed with same posture as in ES, and exercise pattern was set at a 1-s contraction and 1-s relaxation cycle. Exercise intensity was started at 5% MVC (maximal voluntary contraction) and was increased at a rate of 5% MVC/30 sec until exhaustion. In ES and V-Ex, tissue oxygenation index was decreased with decrease in O2Hb (oxy-hemoglobin) and increase in HHb (deoxyhemoglobin), and muscle oxygenation levels at the end of test were very alike. Oxygen consumption, heart rate, systolic and diastolic blood pressure in ES and V-Ex increased significantly, however, the degree of change in ES was significantly lower than V-Ex. Blood lactate was significantly increased in both tests. Adrenaline and noradrenaline were significantly increased in V-Ex, even though they showed no change in ES. These results lead us to believe that ES is an effective technique activated muscle hypoxia and glycolytic pathway metabolism with low stress on respiratory, circulatory and sympathetic nervous systems.

Role of nitric oxide on airway microvascular permeability in patients with asthma.

BACKGROUND: We have recently emphasized that airway microcirculation has the potential to contribute to the pathophysiology of asthma. We therefore hypothesized that increased production of airway nitric oxide (NO) plays an important role in the pathogenesis of asthma through microvascular hyperpermeability. To test our hypothesis, we compared exhaled NO levels in normal subjects and asthmatic patients, and examined the contribution of airway microvascular permeability to the pathophysiology of asthma. METHODS: Inflammatory indexes in induced sputum, exhaled NO levels, and airway vascular permeability index were examined in 11 normal controls, 19 beclomethasone dipropionate (BDP)-treated asthmatics, and 20 BDP-untreated asthmatics. RESULTS: The percentage of eosinophils (% Eos) and concentration of eosinophil cationic protein (ECP) in induced sputum were significantly higher in BDP-untreated asthmatics (% Eos: 16.4 (6.5)%, p < 0.0001; ECP: 674.5 (294.2) ng/mL, p < 0.0001) than in normal controls (0.6 (0.3)%; 112.7 (65.5) ng/mL) and BDP-treated asthmatics (0.7 (0.6)%; 116.3 (72.6) ng/mL). However, exhaled NO levels were significantly higher in BDP-untreated (16.4 (6.9) ppb, p < 0.0001) and -treated (11.2 (3.5) ppb, p = 0.007) asthmatics than in normal controls (5.9 (1.8) ppb). Similarly, airway vascular permeability index was significantly higher in BDP-untreated (0.028 (0.009), p < 0.0001) and -treated (0.016 (0.006), p = 0.005) asthmatics than in normal controls (0.008 (0.003)). We found a significant correlation between exhaled NO level and airway vascular permeability index in both BDP-untreated asthmatics (r = 0.85, p < 0.0001) and -treated asthmatics (r = 0.64, p = 0.0023). Moreover, airway hyperreactivity to methacholine was also significantly correlated with exhaled NO level in BDP-untreated (r = -0.68, p = 0.003) and -treated (r = -0.49, p = 0.037) asthmatics. CONCLUSIONS: Increased production of airway NO is a key factor in the development of airway hyperresponsiveness. Interaction between airway microcirculation and NO may be a key element in disordered airway function in asthma.

Body composition is related to increase in plasma adiponectin levels rather than training in young obese men.

We assessed the major factors regulating adiponectin levels and the influence of exercise training on adiponectin levels in young obese men (19.2 +/- 1.1 yrs, BMI: 31.1 +/- 4.2, %fat: 27.2 +/- 3.9%). Subjects were separated into three groups (aerobic exercise group [AE: n=7], aerobic and resistance exercise group [AE + RE: n = 7], control group [n = 7]). AE underwent an 8-week training program (three times per week, more than 30 min endurance exercise at ventilatory threshold (VT) intensity). AE + RE went through resistance exercise two or three times per week together with the above endurance exercise for 5 months. Prior to intervention (n = 21), adiponectin levels were significantly correlated with percentage of fat. Stepwise multiple regression analysis revealed that percent body fat was an independent predictor of basal adiponectin levels (r2 = 0.370; P<0.01). After intervention, fat mass, and VT were significantly improved in AE. AE + RE exhibited significant reduction in weight, BMI, percent body fat and fat mass, and had significantly increased VT, VO2max cycling power and torque. Insulin was not changed in both groups. The control group exhibited no significant change in any variables. Although adiponectin levels were unchanged in the three groups, a significant negative correlation between delta fat mass and delta adiponectin levels was observed (n = 21, r = -0.461, P<0.05). In addition, delta percent body fat was an independent predictor of delta adiponectin levels (r2 = 0.327, P<0.05). These findings indicate that for increasing the adiponectin level, improvement of the body composition of young obese men is more important than the way training is performed.

Evaluation of peripheral muscle oxygenation during exercise by spatially resolved spectroscopy in patients with chronic obstructive pulmonary disease.

BACKGROUND: Spatially resolved (SR) spectroscopy has enabled non-invasive and continuous measurement of muscle oxygen saturation during exercise. In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction has been widely studied histochemically and biochemically. However, impairment of muscle oxygenation during exercise has not been elucidated yet. METHODS: We measured oxygen saturation in the vastus lateralis muscle (SmO2) using SR spectrometry during incremental cycle exercise in 16 COPD patients and 10 age-matched healthy subjects. RESULTS: Significant decrease in SmO2 was found at peak exercise compared with warm-up in both groups (56.9 +/- 6.0% to 47.3 +/- 6.8% in patients with COPD, p<0.001; 60.7 +/- 5.8% to 49.9 +/- 7.7% in healthy subjects, p<0.01). The decrease in SmO2 was linear with respect to increase in work rate, and the slope of SmO2 was significantly steeper in COPD patients than in healthy subjects (-0.282 +/- 0.159 vs -0.107 +/- 0.057 %/Watt, p<0.001). The slope of SmO2 in COPD patients significantly correlated with body mass index (BMI) (p<0.01), peak percutaneous oxygen saturation (p<0.05), and peak pulmonary oxygen consumption (p<0.05). Stepwise regression analysis revealed that BMI was a significant determinant of the SmO2 slope (p=0.01). CONCLUSIONS: We conclude that oxygenation of peripheral muscle is impaired during exercise in COPD patients and that BMI contributes independently to the change of muscle oxygen saturation with exercise in COPD patients. SR spectroscopy will provide useful information for the study of the dynamics of muscle oxygenation in COPD patients.

Determinants of the severity of exercise-induced bronchoconstriction in patients with asthma.

AIM: In examining the mechanisms of exercise-induced bronchoconstriction (EIB), it is important to determine which factors most strongly affect the severity of EIB. We determined such factors in patients with asthma by stepwise multiple-regression analysis. METHODS: Twenty-three patients with asthma underwent pulmonary function tests, methacholine provocation test, and sputum induction. Eosinophilic inflammatory indices and airway vascular permeability index (ratio of albumin concentrations in induced sputum and serum) were examined in sputum samples, and then an exercise test was performed by all asthmatics. RESULTS: There was a significant correlation between the severity of EIB and degree of eosinophilic inflammation in induced sputum. Moreover, there was a significant correlation between the severity of EIB and airway vascular permeability index. Although we could not find a significant correlation between the severity of EIB and 1-sec forced expired volume, 20% provocation concentration of (PC20) methacholine tended to be correlated with the severity of EIB. By stepwise multiple-regression analysis, we also found that airway vascular permeability index, eosinophil cationic protein levels in sputum, and PC20 methacholine are independent predictors of the severity of EIB. CONCLUSION: We found that airway vascular hyperpermeability, eosinophilic inflammation, and bronchial hyperreactivity are independent factors predicting the severity of EIB.