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ABSTRACT: To understand the mechanism of exertional dyspnea, we postulated that, despite hyperoxia during exercise, patients with idiopathic pulmonary fibrosis (IPF) might not regulate exertional acidosis by ventilatory compensation to stop exercise. The exercise responses during 30% O(2) or compressed air (CA) were examined in 13 patients with IPF. The Pa(O2), Pa(CO2), and H(CO3-) levels were higher during exercise with hyperoxia than with CA. At peak exercise, hyperoxia reduced the plasma lactate level. The dyspnea - ratio (%) of the ΔV˙o(2) (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point with hyperoxia and CA, preceded by a break point in the breathing frequency-ratio of the ΔV˙o(2). Accordingly, the dyspnea score and pH each reached similar levels with hyperoxia and CA to stop exercise. Regardless of breathing CA or 30% O(2), IPF patients did not regulate exertional acidosis by ventilatory compensation to stop exercise, resulting in reaching a specific pH.
Respiratory Physiology & Neurobiology 12/2012; · 2.24 Impact Factor
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Keisuke Miki,
Ryoji Maekura,
Noritoshi Nagaya,
Masamitsu Nakazato,
Hiroshi Kimura,
Shinsuke Murakami,
Shunsuke Ohnishi,
Toru Hiraga,
Mari Miki,
Seigo Kitada, Kenji Yoshimura,
Yoshitaka Tateishi,
Yasuji Arimura,
Nobuhiro Matsumoto,
Masanori Yoshikawa,
Kenichi Yamahara,
Kenji Kangawa
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ABSTRACT: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.
In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated.
In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.
UMIN Clinical Trial Registry C000000061.
PLoS ONE 01/2012; 7(5):e35708. · 4.09 Impact Factor
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ABSTRACT: The results of studies on the oxygen response in patients with COPD should provide important clues to the pathophysiology of exertional dyspnoea. We investigated the exercise responses to hyperoxia in relation to dyspnoea profile, as well as cardiopulmonary, acidotic and sympathetic parameters in 35 patients with stable COPD (mean FEV(1) 46% predicted).
This was a single-blind trial, in which patients breathed 24% O(2) or compressed air (CA) in random order during two incremental cycle exercise tests.
PaO(2) and PaCO(2) were higher (P < 0.0001 and P < 0.05, respectively) at each exercise point while patients were breathing 24% O(2) compared with CA. At a standardized time point near peak exercise, use of O(2) resulted in reduced plasma lactate and plasma noradrenaline concentrations (P < 0.01). Peak minute ventilation/indirect maximum voluntary ventilation was similar while breathing 24% O(2) and CA. At peak exercise, the dyspnoea score, pH and plasma noradrenaline concentrations were similar while breathing 24% O(2) and CA. The dyspnoea-ratio (%) of Δoxygen uptake (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point while breathing 24% O(2) or CA.
Regardless of whether they breathed CA or 24% O(2) , patients with COPD did not develop ventilatory compensation for exertional acidosis, and the pH values measured were similar. Hyperoxia during a standardized exercise protocol did not alter the pattern of exertional dyspnoea in these patients, compared with breathing CA, although hyperoxia resulted in miscellaneous effects.
Respirology 01/2012; 17(1):149-54. · 2.42 Impact Factor
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ABSTRACT: Tiotropium partially relieves exertional dyspnea and reduces the risk of congestive heart failure in chronic obstructive pulmonary disease (COPD) patients. However, its effect on the sympathetic activation response to exercise is unknown.
This study aimed to determine whether tiotropium use results in a sustained reduction in sympathetic activation during exercise.
We conducted a 12-week, open-label (treatments: tiotropium 18 μg or oxitropium 0.2 mg × 3 mg), crossover study in 17 COPD patients. Treatment order was randomized across subjects. The subjects underwent a pulmonary function test and two modes of cardiopulmonary exercise (constant work rate and incremental exercise) testing using a cycle ergometer, with measurement of arterial catecholamines after each treatment period.
Forced expiratory volume in 1 second and forced vital capacity were significantly larger in the tiotropium treatment group. In constant exercise testing, exercise endurance time was longer, with improvement in dyspnea during exercise and reduction in dynamic hyperinflation in the tiotropium treatment group. Similarly, in incremental exercise testing, exercise time, carbon dioxide production, and minute ventilation at peak exercise were significantly higher in the tiotropium treatment group. Plasma norepinephrine concentrations and dyspnea intensity were also lower during submaximal isotime exercise and throughout the incremental workload exercise in the tiotropium treatment group.
Tiotropium suppressed the increase of sympathetic activation during exercise at the end of the 6-week treatment, as compared with the effect of oxipropium. This effect might be attributed to improvement in lung function and exercise capacity and reduction in exertional dyspnea, which were associated with decreases in respiratory frequency and heart rate and reduced progression of arterial acidosis.
International Journal of COPD 01/2012; 7:109-17.
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ABSTRACT: We investigated the susceptibility to conventional and newer antimycobacterial agents including rifabutin (RBT) and novel fluoroquinolones (NFQs) among 48 clinical Mycobacterium avium complex (MAC) isolates from patients with sputum culture-positive MAC disease who were undergoing standard chemotherapy. RBT and NFQs were superior to conventional agents because of higher rates of susceptibility and lower minimum inhibitory concentration. NFQs showed cross-resistance among quinolones. In contrast, RBT did not show cross-resistance to RFP. Most clarithromycin-resistant or rifampicin-resistant cases were susceptible to RBT and NFQs. In conclusion, RBT and NFQs possess good in vitro antimicrobial activity among clinical isolates of culture-positive pulmonary MAC disease, which suggests that a combination of such microbiologically active agents may improve clinical effectiveness more than standard chemotherapy regimens.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 11/2010; 48(11):797-802.
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Seigo Kitada,
Kazuo Kobayashi,
Yukiko Nishiuchi,
Kenji Fushitani, Kenji Yoshimura,
Yoshitaka Tateishi,
Keisuke Miki,
Mari Miki,
Hisako Hashimoto,
Masaharu Motone,
Takeya Fujikawa,
Toru Hiraga,
Ryoji Maekura
Chest 07/2010; 138(1):236-7. · 5.25 Impact Factor
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ABSTRACT: The objective of this study was to investigate whether exertional dyspnea correlates with exercise responses, especially arterial blood pH and plasma norepinephrine (NE) changes, in patients with sequelae of tuberculosis (TBsq). Cardiopulmonary exercise testings were performed in 49 TBsq patients and 9 controls. Each group had a break point in the dyspnea, plasma lactate, and plasma NE changes during exercise, all of which occurred at a similar exercise point. In TBsq patients in both exercise phases before and after the dyspnea break point, the dyspnea-slope (DeltaBorg scale/Deltaminute ventilation) correlated with the pH-slope (DeltapH/Deltaoxygen uptake) (r = -0.616, p < 0.0001; r = -0.629, p < 0.0001, respectively, before and after the break point) and with the NE-slope (DeltaNE/Deltaoxygen uptake) (r = 0.443, p = 0.0012; r = 0.643, p < 0.0001, respectively, before and after the break point). In TBsq patients during exercise, increases in circulating NE levels and exertional acidosis were correlated with exertional dyspnea.
The Journal of Physiological Sciences 05/2010; 60(3):187-93. · 1.61 Impact Factor
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ABSTRACT: Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO(2) and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO(3)(-) levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (DeltaBorg scale/Deltaminute ventilation) correlated with the pH slope (DeltapH/Deltaoxygen uptake) (before the break point: r = -0.537, P = 0.0022; r = -0.886, P < 0.0001, after the break point) and the NE slope (DeltaNE/Deltaoxygen uptake) (before the break point: r = 0.481, P = 0.0075; R = 0.784, P < 0.0001, after the break point).
In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.
Respirology 09/2009; 14(7):1020-6. · 2.42 Impact Factor
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ABSTRACT: The causes of both exertional pulmonary hypertension and pulmonary hypertension in general in chronic obstructive pulmonary disease (COPD) remain to be elucidated. To further understand the pathophysiology in COPD patients, it may be important to recognize the existence of exertional pulmonary hypertension and to determine the severity of exertional hypoxemia. However, little is known about their relationship. To investigate whether the severity of exertional hypoxemia, as evaluated by the Deltaartery oxygen tension/Deltaoxygen consumption (PaO(2)-slope) correlates with the mean pulmonary artery pressure (Ppa), cardiopulmonary exercise testing with haemodynamics was done in 10 patients with moderate to very severe COPD. The PaO(2)-slope was significantly correlated with the mean Ppa from 25% to 40% of the maximum Watts (Wmax), and was most significant at 30% Wmax (r = -0.904, P<0.0001). In this phase, all parameters, except for the mean Ppa and the mixed venous oxygen tension, were not markedly changed from resting levels. At 30% Wmax, the mean Ppa (mean, 27 mmHg) with no or mild hypoxemia was also significantly correlated with the Deltaartery oxygen saturation/Deltaoxygen consumption (SpO(2)-slope) (r = -0.789, P = 0.004). On stepwise multiple regression analysis, the PaO(2)-slope was the most significant predictor of mean Ppa at 30% Wmax. In conclusion, the PaO(2)-slope and the SpO(2)-slope reflect Ppa during the early exercise phase. Thus, assessment of these parameters could be useful to evaluate the cardiopulmonary haemodynamic pathophysiology of COPD patients.
Clinical physiology and functional imaging 01/2008; 28(1):64-9. · 1.21 Impact Factor
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Yukiko Nishiuchi,
Ryoji Maekura,
Seigo Kitada,
Aki Tamaru,
Takahiro Taguri,
Yukimi Kira,
Toru Hiraga,
Atsushi Hirotani, Kenji Yoshimura,
Mari Miki,
Masami Ito
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ABSTRACT: The distribution of Mycobacterium avium-intracellulare complex (MAC) in residences was examined. MAC was only recovered from bathrooms but not from other sites of residences. The appearance ratio in the bathrooms of patients with pulmonary MAC was significantly higher than that in healthy volunteers' bathrooms (P=.01). For 2 patients, the genotypes of environmental isolates were identical to their respective clinical isolates.
Clinical Infectious Diseases 09/2007; 45(3):347-51. · 9.15 Impact Factor
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Yoshinobu Namba,
Seigo Kitada,
Masahide Mori,
Takeo Iwasaki,
Masaharu Motone,
Manabu Niinaka, Kenji Yoshimura,
Mari Miki,
Keisuke Miki,
Nobuyuki Naka,
Toru Hiraga,
Ryoji Maekura,
Masami Ito
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ABSTRACT: A 33-year-old man had a high fever and was given Cefcapene and Oseltamivir without a definite diagnosis of influenza. Three days later an abnormal chest shadow was pointed out. Chest CT revealed ground-glass opacities and air-space consolidation in bilateral lung fields. Although he was given antibiotics, lung infiltrates increased and his symptoms worsened. Therefore, he was transferred to our hospital. Corticosteroid pulse-therapy resulted in prompt improvement of chest infiltrates and his symptoms. The drug-induced lymphocyte stimulating test results indicated 170% of oseltamivir and 150% of cefcapene. Considering the clinical course and laboratory data, this was probably drug-induced lung injury caused by oseltamivir.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 06/2006; 44(5):410-4.
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Keisuke Miki,
Ryoji Maekura,
Toru Hiraga,
Atsushi Hirotani,
Hisako Hashimoto,
Seigo Kitada,
Mari Miki, Kenji Yoshimura,
Nobuyuki Naka,
Masaharu Motone,
Takeya Fujikawa,
Shodayu Takashima,
Rika Kitazume,
Hideaki Kanzaki,
Satoshi Nakatani,
Hirotaka Watanuki,
Osamu Tagusari,
Junjiro Kobayashi,
Masami Ito
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ABSTRACT: We describe a case of infective endocarditis caused by Campylobacter fetus accompanied by pulmonary emboli. A 52-year-old man was referred to our hospital due to febrile temperatures with a history of dental treatment followed by eating raw meat. Computed tomography revealed multiple infiltrations and a nodule with low attenuation area and feeding vessels. A mobile mass, possible vegetation, attached to the tricuspid valve was detected by transthoracic echocardiography. Two blood cultures disclosed Campylobacter fetus. Long-term antibiotic therapy was given, curing the infection with valvuloplasty. We presented the possibility that infective Campylobacter fetus endocarditis after dental treatment was caused by eating raw meat.
Internal Medicine 11/2005; 44(10):1055-9. · 0.94 Impact Factor
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ABSTRACT: We studied whether the serotypes of Mycobacterium avium-Mycobacterium intracellulare complex (MAC) isolates determine the prognosis for pulmonary MAC disease. We prospectively monitored a cohort of 68 patients with pulmonary MAC disease for whom the serotype-specific glycopeptidolipids in isolates were identified using thin-layer chromatography and fast atom bombardment mass-spectrometry in 1990 and 1995. Serovar 4 Mycobacterium avium was detected in 40/68 patients (58.8%). Other serotypes were serotypes 1 (five cases), 6 (three cases), 8 (seven cases), 9 (three cases), 14 (four cases), and 16 (six cases). Patients with serovar 4 were significantly (P < 0.01) younger (63.0 +/- 9.8 years) than patients with other serotypes (71.8 +/- 10.3). Patients who failed treatment had a significantly poorer prognosis than other patients. There were no cases of MAC-related death in the cured group. Chest radiographic findings progressively worsened in 36 (90%) of patients with serotype 4, and 14/36 died from respiratory failure caused by pulmonary Mycobacterium avium disease. The patients with serotype 4 had a significantly poorer prognosis than patients with other serotypes. These results show that both the outcome of chemotherapy and the serotypes of MAC isolates are important for assessing the prognosis of pulmonary MAC disease.
Journal of Clinical Microbiology 07/2005; 43(7):3150-8. · 4.15 Impact Factor
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ABSTRACT: This study examines whether the grading of officially acknowledged respiratory disability reflects exercise disorders in patients with chronic respiratory diseases. In order to do this, we analyzed the cardiopulmonary exercise testing (CPET) data of 258 patients with chronic obstructive pulmonary disease (COPD), 125 with sequela of pulmonary tuberculosis (TB) and 52 with interstitial pneumonia between 1989 and 2002. The peak oxygen uptakes of grade 1 and 3 COPD patients were 12.4 +/- 3.8 and 14.9 +/- 4.3 ml/min/kg (mean +/- SD), respectively. The worse the grade, the lower was the peak oxygen uptake, the differences being significant in COPD patients. Despite this, the peak oxygen uptake range overlapped greatly between grade 1 and grade 3 COPD patients. Sixty percent of patients with TB and 46% of patients with IP whose peak oxygen uptakes were similar to those of grade 1 COPD patients failed to be acknowledged as grade 1. There were no significant differences between the peak oxygen uptake of grade 1 COPD patients and grade 1 TB patients, grade 3 TB patients, and grade 4 IP patients. Patients with TB and IP showed more severe ventilatory and gas exchange disorders than those with COPD. We concluded that the present system of acknowledgement of respiratory disability in Japan did not accurately reflect exercise disorders in patients with chronic respiratory diseases. As well as this, we argue that there is discrimination between patients with COPD, TB and IP. It is necessary to establish an alternative system, reflecting exercise disorders evaluated by CPET to offer a more accurate acknowledgement.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2004; 42(4):299-305.
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ABSTRACT: We have prospectively analyzed three antigens for serodiagnosis of tuberculosis (TB). These antigens were tuberculous glycolipid antigen, lypoarabinomannan polysaccharide antigen, and antigen 60 (A60), which was derived from purified protein derivatives. Of the 131 patients with active pulmonary TB, 57 were both smear and culture negative and 14 had chronic active pulmonary TB that remained smear positive for >12 months of chemotherapy. One hundred twenty healthy adults were controls. The percentages of patients positive in all three tests were 58.8% for smear-positive active pulmonary TB and 71.4% for chronic active pulmonary TB. When the results of the three serodiagnostic tests were evaluated in combination, the sensitivity increased to 91.5% in patients with active pulmonary TB and to 86.0% in smear- and culture-negative patients. The false-positive rate of the three-test combination was 12.5% in the healthy control groups. In conclusion, it was not possible to detect all of the antibodies against antigenic substances in the cell walls of the tuberculous bacilli in the sera of all TB patients by using available serodiagnostic tests. However, the combined use of tests with three separate antigens maximizes the effectiveness of serodiagnosis.
Journal of Clinical Microbiology 03/2004; 42(3):1136-41. · 4.15 Impact Factor
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ABSTRACT: We studied the relationship between physiologic parameters in cardiopulmonary exercise testing (CPET) and prognosis in terms of survival time in patients with chronic obstructive pulmonary disease (COPD) in order to accurately assess the severity of the disease. From a group of 195 patients with COPD who had consecutively undergone CPET between July 1989 and October 1997, we enrolled 120 subjects (mean age 67.6 years, 104 males) with exertional dyspnoea into a cohort protocol. Of these subjects, 34 (28.3%) died during the 3-5-year follow-up period after CPET. By univariate analysis, the following factors were significantly associated with survival time: age, body mass index, %FVC, %FEV1, FEV1%, PaCO2 at rest, severity of exercise-induced hypoxemia evaluated by DeltaPaO2/DeltaVO2 (PaO2-slope), oxygen uptake, ventilation, tidal volume, PaCO2 and oxygen pulse at maximum exercise, as well as prescribing long-term oxygen therapy. By multivariate analysis, age and the PaO2-slope showed significance as independent prognostic factors, and the PaO2-slope was most closely associated with the survival time. These results reveal that CPET is a useful technique to accurately assess the relationship between the functional impairments and the prognosis of patients with COPD.
Clinical physiology and functional imaging 12/2003; 23(6):324-31. · 1.21 Impact Factor
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ABSTRACT: In Japan, long-term care insurance (LTCI) for the elderly has been available since April 2000. Eligibility levels for LTCI for patients with home oxygen therapy (HOT) was investigated for two periods during a 20-month interval between April 2000 and December 2001. During these periods, we hosted a seminar on respiratory care, taking the form of a special report on the daily life of HOT patients. This report was submitted to an expert committee in order to inform the members of the committee about the characteristics of HOT patients. Of 76 HOT patients who had utilized visiting-nurse services, 58 applied for an assessment for LTCI eligibility. The levels determined were less than those expected by the patients' doctors (Categories: Not fulfilling the criteria, seven cases; Rejected, 13 cases; Assistance-required, six cases; Care-required, level 1, 14 cases; Care-required, level 2, 10 cases; Care-required, level 3, three cases; Care-required, level 4, three cases; and Care-required, level 5, two cases). As many as six of the 27 patients who used home mechanical ventilation were rejected. There were also patients who were forced to stop the care services that they had been receiving. Forty patients, including eight who applied for a re-assessment, were finally assigned to a Care-required category. The home-help service was the most frequently utilized (35.0%). Day services, short stay, and the visiting-bathing service, which are commonly used for patients with cerebral apoplexy sequela, were not needed nearly as much (5.0%, 2.5%, 2.5%, respectively). The eligibility levels at the second point of evaluation were higher than those at the first point in 37.5% of the patients, and equal in 58.3%. In the 39 new-applicant patients at the second point of evaluation, the ratio of Care-required patients was significantly increased (62.7% to 72.2%, p < 0.05). The eligibility level is primarily decided by computer using a score derived from a form that contains 73 questions about the physical condition of the applicant. However, this information is inadequate for a precise assessment of the impairment of the HOT patients. The final decision on a patient is made by an expert committee, based on both the primary result and the report of the doctor in charge of that patient. It may be effective to inform the members involved in the final decision about the characteristics or special needs resulting from the disease that necessitates HOT. However, we believe that it may be more important to find a way to increase the validity of the primary judging. We would argue that a method for proper assessment of HOT patients should be designed.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 06/2003; 41(6):377-81.
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ABSTRACT: Evaluation of possible cardiac complications is essential for safe and effective respiratory rehabilitation of patients with chronic respiratory diseases (CRDs). The aim of this study is to clarify the pathophysiology of electrocardiographic (ECG) changes during exercise and the prevalence of coronary artery disease (CAD) in CRD patients without a history of myocardial ischemia.
We studied 42 CRD patients with exercise-induced ST depression by cardiopulmonary exercise testing (CPET). They were selected from 249 consecutive CRD patients without any history of CAD who underwent CPET between January 1999 and December 2001. Thirty-three patients without respiratory diseases who had positive ST depression during exercise were selected as disease control subjects. Exercise myocardial SPECT was performed to evaluate myocardial ischemia and right ventricular (RV) overload as measured by increased RV uptake.
Among the 249 consecutive CRD patients without any history of CAD, positive ST depression during exercise was found in 42 (16.9%). Only 2 of the 42 patients (4.8%) had an ST depression other than in II, III, or aVF leads. The incidence of myocardial ischemia by perfusion SPECT was significantly lower in CRD patients (26.2%) than in disease control subjects (78.8%). The most common finding in the CRD patients during exercise was RV overload but without ischemia (26 cases; 61.9%). Ischemia was found in 11 patients (26.2%), with 10 of these patients also having RV overload. Neither ischemia nor RV overload was found in 5 patients (11.9%); these patients were eventually diagnosed as normal.
The incidence of myocardial ischemia as determined by perfusion SPECT was low in CRD patients with positive exercise-induced ECG changes. On the other hand, RV overload was observed in most such cases. Cardiac perfusion SPECT is a useful technique to evaluate cardiac ischemia and RV overload simultaneously. CPET with 12-lead ECG monitoring is necessary in CRD patients before respiratory rehabilitation. Further examination for ischemia should be done if positive ST depression is found.
Journal of Nuclear Medicine 04/2003; 44(3):325-30. · 6.38 Impact Factor
