[Reduced ADL, QOL and musculoskeletal dysfunction associated with respiratory disease.]

Chronic respiratory disease, such as chronic obstructive pulmonary disease(COPD)continues to cause a heavy health and economic burden in the world. Lower-limb muscle dysfunction is a prominent and major extrapulmonary features in individuals with moderate-to-very severe COPD and has important clinical implications, such as reduced exercise tolerance, activity of daily living(ADL), health related quality of life(HRQOL)and even survival. Osteoporosis is also an important systemic feature of COPD. Osteoprotic fracture cause many symptoms and complications, including the impairment of ventilation, and create a heavy economic burden. Comprehensive treatments(drug medication and non-drug treatment)for these impairments, such as pulmonary rehabilitation, are recommended. Pulmonary rehabilitation improves dyspnea, exercise capacity, ADL, and HRQOL, each of which is recognized predictors of mortality.

Osteoporosis is highly prevalent in Japanese males with chronic obstructive pulmonary disease and is associated with deteriorated pulmonary function.

Osteoporosis has recently been recognized as a major comorbidity in chronic obstructive pulmonary disease (COPD). We conducted a cross-sectional study in a cohort of 136 Japanese males with COPD to evaluate the prevalence of vertebral fracture (VF) and to explore its relationship with pulmonary function parameters. VFs were present in 108 (79.4%); multiple and severe (SQ grade 2 or 3) VFs were found in 77 (56.6%) and 25 (18.4%), respectively. Multivariate logistic regression analyses revealed that decrease in forced expiratory volume in one second (FEV1.0)/forced vital capacity (FVC) [odds ratio (OR) 0.963, 95% confidence interval (CI) 0.929-998, p = 0.036] was associated with the presence of VF after adjustment for age and that FVC (OR 0.462, 95% CI 0.220-0.968, p = 0.041) and current smoking (OR 2.992, 95% CI 1.128-7.940, p = 0.028) were associated with VF severity (grade 2-3 vs. 1). We also found that FEV1.0 was the sole independent determinant of the number of VFs by stepwise multivariate linear regression (p < 0.001). Bone mineral density (BMD) values were available in 49 subjects. Mean T scores were -2.0 ± 1.2 in femoral neck, -1.4 ± 1.2 in total hip and -1.1 ± 1.4 in lumbar spine. Nineteen patients (38.8%) had a BMD T score less than -2.5. BMD Z scores of all the sites showed a progressive decrease as GOLD stage of COPD advanced (p < 0.05). Our results indicate a high prevalence of osteoporosis in Japanese male COPD patients and a strong inter-relationship between the two diseases, re-emphasizing the urgent need for appropriate intervention to maintain both bone and lung health.

[Arterial blood gas analysis, pulse oximeter].

We inspire air and get oxygen, and the storaging conditions of the oxygen in the blood are gas and solid (Hb-O2) type. To measure the gas type oxygen in the blood, we use blood gas analyzing meters, and we also can measure solid type oxygen by this method. From this method, we can get arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), pH, HCO3(-), and so on. By the way, pulse oximeter is an equipment to measure percutaneous arterial oxygen saturation (SpO2). Although the PaO2 and SpO2 are essential parameters to know the clinical conditions of COPD patients, we should be aware of the primary differences between them, and use these parameters effectively.

Chronic pulmonary toxicity study of indium-tin oxide and indium oxide following intratracheal instillations into the lungs of hamsters.

OBJECTIVES: The aim of this study was to clarify the chronic toxicological effects of indium-tin oxide (ITO) and indium oxide (In(2)O(3)) on laboratory animals. METHODS: Male Syrian golden hamsters were intratracheally administered 3 mg/kg or 6 mg/kg of ITO particles, or 2.7 mg/kg or 5.4 mg/kg of In(2)O(3) particles, containing 2.2 mg/kg or 4.5 mg/kg of indium, twice a week, for 8 wk. Control hamsters were given vehicle of distilled water only. The hamsters were euthanized serially up to 78 wk after the final instillation and the toxicological effects were determined. RESULTS: Body weight gain was significantly suppressed in the ITO 6 mg/kg-treated hamsters compared with the control group, but not in the ITO 3 mg/kg-treated or In(2)O(3)-treated hamsters. Relative lung weights among all the indium-treated groups were significantly increased compared to that in the control group throughout the observation period. The serum indium concentration among all the indium-treated groups gradually increased up to the end of the observation period. Histopathologically, foci of slight to severe pulmonary inflammatory response with diffuse alveolar or bronchiolar cell hyperplasia, expansion of the alveolar spaces and interstitial fibrotic proliferation were present in all the indium-treated hamsters and the severity of these lesions worsened with the passage of time. Lung benign adenomas were only manifest in 3 out of 15 of the ITO 6 mg/kg-treated hamsters. CONCLUSIONS: The present results clearly demonstrate that ITO and In(2)O(3) particles caused chronic pulmonary toxicity when repeated intratracheal instillations were given to hamsters.

Decreased ventilatory response to hypercapnia in dementia with Lewy bodies.

A systematic autonomic dysfunction observed among patients with dementia with Lewy bodies (DLB) has recently attracted close attention. Here, we compare cardiovascular and pulmonary autonomic functions among patients with DLB, patients with Alzheimer's disease, and healthy control subjects. All 15 DLB patients demonstrated severely low ventilatory response to hypercapnia, whereas none of the other subjects demonstrated abnormal results. The majority of the DLB patients showed impaired heart rate variability, low uptake on (123)I-metaiodobenzylguanidine myocardial scintigraphy, and orthostatic hypotension. Ventilatory response to hypercapnia as a marker of respiratory autonomic function is a promising diagnostic tool for DLB.

Effects of aerobic training and recreational activities in patients with chronic obstructive pulmonary disease.

The purpose of this study was to evaluate whether strength or recreational activities are a useful addition to aerobic training in patients with chronic obstructive pulmonary disease (COPD). Thirty-three patients with moderate to severe COPD were randomly assigned to 12 weeks of aerobic combined with strength training (AERO+ST) or combined with recreational activities (AERO+RA). The AERO regimen consisted of three weekly 20-min walking exercise sessions; the ST regimen included three series of 10 repetitions of four exercises; and the RA regimen consisted of training using exercise balls to perform smoothly for instrumental activity of daily living. Baseline and after-training measurements of peripheral muscular strength and endurance, cardio respiratory fitness, and 6-min walking distance were obtained, whereas quality of life was assessed with the Short Form 36 questionnaire. Change in grip strength showed a significant difference between the AERO+ST group (8.3+/-6.7%) and the control group (-1.3+/-10.5%), and AERO+RA group (-4.7+/-5.6%) (P<0.05). A significant increase was found in percentage change in peak (.)V(O2) between the AERO+ST group (5.1+/-11.8%) and the control group (-9.2+/-8.6%) (P<0.05). In the health-related quality of life scores, there was a significant difference in mean percentage change in physical functioning between the AERO+ST group (7.9+/-24.4%) and the control group (-14.8+/-19.1%) (P<0.05). A significant difference was found in mean percentage change in social functioning between the AERO+RA group (9.4+/-20.0%) and the control group (-14.9+/-23.2%) (P<0.05). A significant difference in mean percentage change in mental health was also found between the AERO+RA group (12.2+/-12.4%) and the control group (-5.0+/-7.8%) (P<0.05). It is preferable to introduce various forms of exercise that use different muscles involving the whole body, such as recreational activities, as they are an appropriate approach to stimulating physical activity and to improving functional fitness gradually while improving health-related quality of life, though it is necessary to practice exercises for maintenance and improvement in patients with COPD.

[Respiratory chemosensitivity in dementia with Lewy bodies].

The incidence of dementia with Lewy bodies (DLB) is increasing rapidly due to the increasing longevity of the population. In DLB, autonomic dysfunction, such as sleep disorders, and cardiopulmonary arrest, together with unconsciousness, can occur. Such cases have poor prognosis and may have dysfunction of chemosensitivity in the respiratory center. We have assessed the function of the respiratory center, especially chemosensitivity to hypercapnia. Twelve probable DLB patients (Group 1) and twelve age-matched healthy subjects (Group 2) were examined. Chemosensitivities to hypercapnia expressed by delta expiratory volume/delta partial pressure of carbon dioxide/body surface area: mean 0.16 (1/min/Torr/m(2)) in Group 1 and 0.49 in Group 2. Thus, patients with DLB had a subnormal hypercapnic response in chemosensitivity of the respiratory center, suggesting dysfunction of the respiratory center. Respiratory center dysfunction may be related to cardiopulmonary arrest together with unconsciousness, so, patients with DLB should not use drugs affecting the respiratory center.

Sleep stage determines the expression pattern of sleep apneas.

We report on an obese man with sleep stage-dependent apnea. His type of apnea was predominantly central during non-rapid eye movement (NREM) sleep, while it was obstructive during rapid eye movement (REM) sleep. We found significantly more and more severe apneas during REM sleep compared to NREM sleep. His apneas were remarkably reduced by position adjustment, suggesting that upper airway collapse played a key role in the induction of both types of apnea. As his apneic patterns were dependent on the sleep stages, we assumed that the balance between upper airway obstruction and instability of central respiratory control might be important in determining the expression types.

A new, simple stapling technique for pulmonary emphysema: its effects and safety for improving respiratory function.

PURPOSE: We performed lung volume reduction surgery (LVRS) in an experimental model using a simple stapling technique (SST) for pulmonary emphysema. The technique uses a stapler to isolate the affected lung from the remaining lung instead of removing it. We performed the present experiment using dogs to study the effects and safety of LVRS using the SST. METHODS: Pulmonary emphysema was induced in 12 dogs with papain. They were divided into three groups: those operated on with SST composed the operation (Op) group; those receiving an experimental thoracotomy composed the sham-operation (Sham-op) group; and those not operated on composed the nonoperation (Non-op) group. Respiratory function was compared among the groups before induction of emphysema (baseline), after induction of emphysema (preoperation), and at 8 weeks after the operation (postoperation Op and Sham-op groups only). The lung was removed and histologically examined 8 weeks after the SST operation. RESULTS: In the Op group, alteration in forced expiratory volume (FEV) 0.5%, airway resistance (Raw) and specific airway conductance (sGaw) showed significantly favorable results. Histologically, the isolated area was widely replaced by fibrous tissue with numerous blood vessels in the circumference in the Op group; no signs of infection such as polykaryoleukocytes or microabscesses were observed in any of the samples. CONCLUSION: The LVRS for pulmonary emphysema using a simple stapling technique improved the expiratory flow and alleviated airway resistance. The isolated remaining lung was well organized without any infectious events or secondary adversity, thus demonstrating the safety of this technique. From these results, this technique is therefore suggested to be effective and applicable to clinical use.

Airway hyperresponsiveness induced by cationic proteins in vivo: site of action.

Major basic protein and other native cationic proteins increase airway hyperresponsiveness when administered to the luminal surface of the airways in vitro. To determine whether the same applies in vivo, we assessed airway responsiveness in rats challenged with both aerosolized and intravenously infused methacholine. We partitioned total lung resistance into its airway and tissue components using the alveolar capsule technique. Neither poly-l-lysine nor major basic protein altered baseline mechanics or its dependence on positive end-expiratory pressures ranging from 1 to 13 cmH(2)O. When methacholine was administered to the lungs as an aerosol, both cationic proteins increased responsiveness as measured by airway resistance, tissue resistance, and tissue elastance. However, responsiveness of all three parameters was unchanged when the methacholine was infused. Together, these findings suggest that cationic proteins alter airway responsiveness in vivo by an effect that is apparently limited to the bronchial epithelium.

Determinants of cardiorespiratory fitness in patients with chronic obstructive pulmonary disease, focusing on activities parallel to daily living.

OBJECTIVE: The purpose of this study was to examine whether activities parallel to daily living (APDL) constitute a determinant index of cardiorespiratory fitness in patients with chronic obstructive pulmonary disease (COPD). METHODOLOGY: Four functional physical fitness parameters were investigated in 38 male patients (mean age 69.8 +/- 6.7 years) with moderate to severe COPD. The parameters measured were muscular strength (grip strength), muscular endurance strength (arm curl, keeping a half-squat position) and regulation (walking around two cones). In addition, cardiorespiratory fitness was measured using a 6-min walking distance test (6MWD) and peak oxygen uptake (VO(2peak)) was measured during bicycle ergometer testing. Maximal inspiratory pressure (MIP) and maximal expiratory pressure were measured so as to quantify respiratory muscle strength. RESULTS: There were significant correlations (P < 0.05) between the VO(2peak), muscular endurance, pulmonary function and respiratory muscle strength. There were also significant correlations of VO(2peak) to muscular endurance, muscular strength, muscular endurance strength and regulation. In stepwise multiple regression analysis, per cent predicted forced expiratory volume in 1 s and MIP appeared to be significant determinants of VO(2peak), showing a total variance of 56% (P < 0.05). For the 6MWD, the significant determinants were forced vital capacity, MIP and performance in the half-squat test, showing a variance of 59% (P < 0.05). CONCLUSION: The results suggest that cardiorespiratory fitness is strongly affected by MIP, pulmonary function and muscular endurance strength, as APDL depend on lower-limb use.

Circuit training for elderly patients with chronic obstructive pulmonary disease: a preliminary study.

To examine the efficacy of the circuit training in elderly patients with chronic obstructive pulmonary disease (COPD), we evaluated muscle forces of the upper and lower extremities and respiratory muscles, exercise tolerance and quality of life (QOL) before and after the circuit training in 10 male patients with mild to severe COPD. The circuit training improved muscle forces of the upper and lower extremities and abdominal muscles (P < 0.05), and 6 min walking distance (P < 0.05). Emotional function and mastery in the Chronic Respiratory Disease Questionnaire scores (P < 0.05) were also improved after the circuit training. The circuit training designed in the present study was effective to improve the QOL in elderly COPD patients.

Effect of heavy-ion radiotherapy on pulmonary function in stage I non-small cell lung cancer patients.

STUDY OBJECTIVES: The purpose of this study was to investigate the effect of heavy-ion radiotherapy on pulmonary function in patients with clinical stage I non-small cell lung cancer (NSCLC) patients. DESIGN: Retrospective study. SETTING: Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan. PATIENTS: From a total of 81 patients who were not candidates for surgical resection due to medical reasons or patient refusal, and who were treated with carbon beam radiotherapy from October 1994 to February 1999, the 52 patients who had completed the repeat overall pulmonary function tests at 6 and 12 months after undergoing heavy-ion radiotherapy were examined. The total heavy-ion irradiation dose ranged from 59.4 to 95.4 photon gray equivalents (GyE), with a mean dose of 76.2 GyE. INTERVENTIONS AND MEASUREMENT: Pulmonary function was evaluated prior to heavy-ion radiotherapy and at 6 and 12 months after heavy-ion radiotherapy. Comparisons of all pulmonary function indexes between, before, and at 6 and 12 months after heavy-ion radiotherapy were made using repeated-measures analysis of variance using the Dunnett test for post hoc comparison. RESULTS: A statistically significant decrease in FEV(1) and total lung capacity was detected at both 6 and 12 months after the patient had undergone heavy-ion radiotherapy. No significant decreases in other pulmonary function indexes in patients were observed at either 6 or 12 months after heavy-ion radiotherapy. The magnitude of the decrease in all pulmonary function indexes was < 8% at both 6 and 12 months after heavy-ion radiotherapy. CONCLUSIONS: These findings suggest that heavy-ion radiotherapy is feasible for stage I NSCLC patients without a severe loss of pulmonary function.

Radiotherapy for elderly non-small cell lung cancer patients.

Elderly patients with lung cancer tend to have significant coexisting diseases and less aggressive treatment is often required. To investigate the clinicopathological features of non-small cell lung cancer (NSCLC) in elderly patients who were treated with radiotherapy, we reviewed the medical records at our division. Among the 189 patients 70 years or older between 1992 and 2001, 28 (14.8%) patients were treated with radiotherapy (elderly group). In the elderly group, there was a medical history of chronic obstructive pulmonary disease (COPD) (57.1%), cardiovascular disease (32.1%), diabetes mellitus (18.5%), malignant disease (18.5%), or cerebrovascular disease (10.7%). Moreover, in the elderly group, 17 (60.7%) patients had two or three coexisting diseases. There was statistical difference between the elderly group and the younger group (less than 70 years patients) with regard to COPD (p<0.001). Also there was statistical difference between the elderly group and the younger group with regard to number of coexisting diseases (p=0.002). In the elderly group, forced expiratory volume in one second (FEV1), forced expiratory volume (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (DLCO) were statistically significant impaired to compare with those in the younger group (p<0.001, p=0.030, p<0.001 and p=0.024, respectively). In the elderly group, 10.7% of patients had concurrent chemoradiotherapy, however, 38.5% of patients of the younger group received concurrent chemoradiotherapy. There was a statistical difference between the two groups (p=0.026). Adequate palliative care to provide prolonged quality survival is an appropriate primary goal of therapy for lung cancer in the elderly and radiotherapy is thought be one of the less invasive treatments.

Age-related changes in plasma orexin-A concentrations.

To study the effect of aging on orexin-A, we measured plasma orexin-A concentrations in 82 healthy volunteers (55 men and 27 women) over a wide range of ages (mean 50.2 +/- 13.9 years, ranging from 23 to 79 years). Correlation analyses revealed that plasma orexin-A concentrations correlated with age (r = 0.50, P < 0.01). When comparing three age groups, it appeared that the concentrations in the group of more than 60 years were significantly higher than those in the group of less than 39 years in both genders (P < 0.05). These findings suggest that orexin-A could be involved in aging in a healthy population.