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Background : Streptococcus pneumoniae is one of the most common bacteria identifi ed in sputum obtained from subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Purpose : To examine the urinary pneumococcal antigen test in subjects admitted with AECOPD and subjects with COPD, and to evaluate its relationship with AECOPD. Methods: Urine samples from 82 subjects with AECOPD involved in 122 consecutive hospitalizations were tested. Additionally, 196 consecutive subjects with stable COPD were tested a total of 607 times at intervals greater than 6 months. Results: Pneumococcal antigen was positive in 14 (17.1%) out of all 82 subjects fi rst hospitalized with AECOPD. It was positive in 7 (20.6%) out of the 34 subjects with pneumonic exacerbations of COPD, and in 7 (14.6%) out of the 48 subjects with non-pneumonic exacerbations of COPD. Two subjects with non-pneumonic S. pneumoniae-related AECOPD were identifi ed, and they both tested positive. A total of 607 urinary antigen tests were performed on stable COPD subjects, and 16 (2.6%) specimens were positive. Colonization by S. pneumoniae was found in the sputum of only 25% of the COPD subjects with positive urinary pneumococcal antigen test results. Conclusion: The results of the pneumococcal urinary antigen test were similar for AECOPD subjects with and without pneumonia. This test may be a useful method for preventing the under-diagnosis of S. pneumoniae-related exacerbations of COPD. The detection of pneumococcal antigen in the urine is not related to the persistent colonization of the respiratory mucosa by S. pneumoniae.

The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA. This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry. In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum. Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.

Background Dyspnea while performing the activities of daily living has been suggested to be a better measurement than peak dyspnea during exercise. Furthermore, the inspiratory capacity (IC) has been shown to be more closely related to exercise tolerance and dyspnea than the FEV1, because dynamic hyperinflation is the main cause of shortness of breath in patients with COPD. However, breathlessness during exercise is measured in most studies to evaluate this relationship. Purpose To evaluate the correlation between breathlessness during daily activities and airflow limitation or static hyperinflation in COPD. Methods We examined 167 consecutive outpatients with stable COPD. The Baseline Dyspnea Index (BDI) was used to evaluate dyspnea with activities of daily living. The relationship between the BDI score and the clinical measurements of pulmonary function was then investigated. Results The Spearman rank correlation coefficients (Rs) between the BDI score and the FEV1(L), FEV1(%pred) and FEV1/FVC were 0.60, 0.56 and 0.56, respectively. On the other hand, the BDI score also correlated with the IC, IC/predicted total lung capacity (TLC) and IC/TLC (Rs = 0.45, 0.46 and 0.47, respectively). Although all of the relationships studied were strongly correlated, the correlation coefficients were better between dyspnea and airflow limitation than between dyspnea and static hyperinflation. In stepwise multiple regression analyses, the BDI score was most significantly explained by the FEV1 (R2 = 26.2%) and the diffusion capacity for carbon monoxide (R2 = 14.4%) (Cumulative R2 = 40.6%). Static hyperinflation was not a significant factor for clinical dyspnea on the stepwise multiple regression analysis. Conclusion Both static hyperinflation and airflow limitation contributed greatly to dyspnea in COPD patients.

Toru Oga1, Mitsuhiro Tsukino2, Takashi Hajiro3, Akihiko Ikeda4, Koichi Nishimura5 1Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Department of Respiratory Medicine, Hikone Municipal Hospital, Hikone, Japan; 3Department of Respiratory Medicine, Tenri Hospital, Tenri, Japan; 4Department of Respiratory Medicine, Nishi-Kobe Medical Center, Kobe, Japan; 5Department of Respiratory Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan Background: Chronic obstructive pulmonary disease (COPD) is considered to be a respiratory disease with systemic manifestations. Some multidimensional staging systems, not based solely on the level of airflow limitation, have been developed; however, these systems have rarely been compared. Methods: We previously recruited 150 male outpatients with COPD for an analysis of factors related to mortality. For this report, we examined the discriminative and prognostic predictive properties of three COPD multidimensional measurements. These indices were the modified BODE (mBODE), which includes body mass index, airflow obstruction, dyspnea, and exercise capacity; the ADO, composed of age, dyspnea, and airflow obstruction; and the modified DOSE (mDOSE), comprising dyspnea, airflow obstruction, smoking status, and exacerbation frequency. Results: Among these indices, the frequency distribution of the mBODE index was the most widely and normally distributed. Univariate Cox proportional hazards analyses revealed that the scores on three indices were significantly predictive of 5-year mortality of COPD (P < 0.001). The scores on the mBODE and ADO indices were more significantly predictive of mortality than forced expiratory volume in 1 second, the Medical Research Council dyspnea score, and the St. George's Respiratory Questionnaire total score. However, peak oxygen uptake on progressive cycle ergometry was more significantly related to mortality than the scores on the three indices (P < 0.0001). Conclusion: The multidimensional staging systems using the mBODE, ADO, and mDOSE indices were significant predictors of mortality in COPD patients, although exercise capacity had a more significant relationship with mortality than those indices. The mBODE index was superior to the others for its discriminative property. Further discussion of the definition of disease severity is necessary to promote concrete multidimensional staging systems as a new disease severity index in guidelines for the management of COPD. Keywords: COPD, multidimensional staging systems, BODE index, ADO index, DOSE index&nbsp

Objective We identified the prognostic relevance of pneumothorax in interstitial lung disease (ILD) patients and evaluated the efficacy and safety of autologous blood-patch pleurodesis. Methods We retrospectively reviewed 59 occurrences of pneumothorax in 34 ILD patients identified over a 12-year period. Results Air leakage ceased in 16 of 22 (72.7%) episodes after blood pleurodesis and in 11 of 14 (78.6%) episodes after chemical pleurodesis. Both the cure ratio and recurrence ratio in the cure episodes were comparable with those in the chemical pleurodesis group (p=0.99 and 0.99, respectively). In addition, there were no harmful events associated with blood pleurodesis. The median survival time after the first episode of pneumothorax was less than 9 months in patients with idiopathic interstitial pneumonia (IIP) and only around 3 years in the patients with other types of ILD, which have essentially favorable outcomes. Kaplan-Meier survival estimates were significantly worse in the patients with concomitant pneumomediastinum than in those without (p

Background Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ. Findings The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement. Conclusions The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.

Obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure. Significant decreases were reported in blood pressure of hypertensive OSA patients with sleepiness who underwent continuous positive airway pressure (CPAP) treatment, but not in non-sleepy hypertensive OSA patients. More recently, however, significant decreases in blood pressure in non-sleepy hypertensive OSA patients following CPAP were shown. Effects of sleepiness on hypertension in OSA patients have been investigated, but not the effects of hypertension on sleepiness in OSA patients. We investigated the relationships between hypertension and sleepiness in patients with OSA. We analysed data on 275 middle-aged male subjects from a cross-sectional epidemiological health survey. We measured blood pressure and sleep duration objectively using an actigraph for 7 days and the respiratory disturbance index (RDI) with a type 3 portable device for 2 nights, and assessed sleepiness using the Epworth Sleepiness Scale (ESS). The RDI correlated significantly with ESS scores in the 88 hypertensive subjects (r = 0.33, P = 0.0024), but not in the 187 non-hypertensive subjects (r = -0.01, P = 0.91). Short sleep duration correlated significantly with ESS scores in both groups. Both the RDI and short sleep duration were related independently to sleepiness in only hypertensive subjects. Furthermore, the RDI was related negatively significantly to sleep duration in hypertensive subjects. Although short sleep duration was related significantly to sleepiness in both groups, hypertension may be important for the sleepiness in OSA patients. Detailed mechanisms of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension should be studied further.

Hepatopulmonary syndrome (HPS) is defined as hypoxemia induced by intrapulmonary vascular dilations associated with liver disease. Although liver transplantation (LT) is the only effective therapy established for severe HPS, patients with a partial pressure of arterial oxygen (PaO(2) ) less than 60 mm Hg have a poor prognosis. We treated a 4-year-old boy with HPS whose preoperative PaO(2) level was 48.8 mm Hg. After LT, he had persistent severe hypoxemia, although he was receiving high-flow oxygen. Noninvasive ventilation (NIV) was introduced, and his respiratory insufficiency promptly improved. Therefore, NIV therapy immediately after extubation following transplantation was administered to the next 4 consecutive HPS patients whose preoperative PaO(2) was less than 60 mm Hg. The NIV treatment of these 5 patients could have been responsible for preventing severe postoperative complications as well as reintubation and hospital death. NIV therapy for both pediatric and adult patients with severe HPS immediately after extubation might protect them from severe hypoxemia after transplantation and from complications necessitating reintubation and might improve their prognosis.

Summary Background Obstructive sleep apnea (OSA) has both systemic and local effects partly through the increased oxidative stress caused by intermittent hypoxia and reoxygenation. However, lung-specific biomarkers in OSA have not been fully assessed in comparison with systemic biomarkers such as C-reactive protein (CRP), although results of a recent study having a small sample size indicated KL-6 as one candidate. Methods Subjects of the present study were 197 patients suspected to have OSA. In addition to polysomnography, we also measured serum levels of KL-6, surfactant protein-D (SP-D) and CRP and pulmonary function. We examined the relationships of different biomarkers with OSA severity and pulmonary function. Results The apnea/hypopnea index (AHI) was significantly positively correlated with serum KL-6 levels even after adjustment for body mass index (BMI) and smoking ( p = 0.03), but not with SP-D and CRP. Also, a significant trend for an increase in serum KL-6 was noted in accordance with the severity of OSA even after adjustment for BMI and smoking ( β coefficient = 0.18, p = 0.02). Additionally, elevated KL-6 levels were significantly associated with restrictive lung function disturbance and gas exchange derangement after adjustment for obesity and smoking, which contrasted with CRP whose elevations were significantly associated with worsened airflow limitation and increased lung volume. Conclusions Serum KL-6 levels may reflect the degree of subclinical lung injury associated with OSA independently of obesity or smoking, unlike CRP. We consider that KL-6 can be a potential candidate as a lung-specific biomarker of OSA and might provide complementary information on systemic biomarkers in assessing OSA.

Background Pulmonary complications are associated with increased mortality after liver resection. Although noninvasive ventilation (NIV) has proved to be an effective treatment for respiratory failure after abdominal surgery, including organ transplantation, its efficacy for pulmonary complications following liver resection per se has not been reported. The aim of this retrospective study was to investigate the effects of NIV in patients with postoperative pulmonary complications after liver resection. Methods A retrospective single center study. Between April 2002 and March 2005, we used NIV in 16 patients who met the criteria for NIV after liver resection: respiratory failure and/or a massive atelectasis (NIV group). We also reviewed data on 10 patients who underwent liver resection from April 1999 to March 2002, and met the criteria for NIV after the operation and received conventional treatment (non-NIV group). Results Respiratory-cause mortality was significantly lower in NIV group than in non-NIV group (0.0% vs. 40.0%, p=0.007), and all-cause mortality tended to be lower in NIV group (18.8% vs. 50.0%, p=0.100). After NIV treatment for 24 hours, the PaO2/FiO2 ratio and PaCO2 were improved significantly but no significant improvement was noted in non-NIV group. Rate of reintubation was significantly lower in NIV group (12.5% vs. 50.0%, p=0.040). NIV was tolerated in all 16 NIV group patients, and no severe NIV-related complications were observed. Conclusion NIV is effective in patients with respiratory failure and/or massive atelectasis after liver resection.

Maintaining alertness during noninvasive positive pressure ventilation (NPPV) is important, but there are no established guidelines for the use of sedation. We report our first experience of an infant with post-surgical vocal cord paralysis, severe stridor and breathing difficulties, who was reintubated after NPPV treatment without sedation, but who avoided a third reintubation through the use of sedation with the second NPPV treatment. NPPV treatment with the proper sedation can improve blood gas data in those patients with severe dyspnea, which can occur during respiratory care in several situations, and can affect not only infants, but also adults including elderly patients.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders in humans. The most frequent CAH variant is 21-hydroxylase deficiency. Patients with 21-hydroxylase deficiency require long-term glucocorticoid replacement treatment. Although sleep disturbance is frequently observed under glucocorticoid replacement treatment, a case of obstructive sleep apnea(OSA) in patients with CAH has not been reported.A 43-year-old man with CAH who complained about sleep disturbance and sleep bruxism was diagnosed as obstructive sleep apnea (OSA) by polysomnography (PSG). Following the introduction of nasal continuous positive airway pressure (nCPAP), his sleep disturbance with symptoms also improved; in addition, he was able to reduce the dose of glucocorticoid replacement therapy without any adverse consequences on his sleep pattern.Physicians who treat a patient with CAH should know the possibility in the existence of OSA in their patients. Because symptoms with OSA in CAH patient may increase the dosage of long-term glucocorticoid treatment for the patient, which may induce several adverse effects including body weight gain on the patient.

OBSTRUCTIVE SLEEP APNEA (OSA) IS CHARACTERIZED BY REPEATED EPISODES OF APNEA AND HYPOPNEA DURING SLEEP. THERE IS A GROWING BODY OF evidence to support the belief that severe OSA is a risk factor for cardiovascular diseases and death,1 not only in clinical cases2,3 but also in the general population.4,5 The National Cholesterol Education Program (NCEP) Adults Treatment Panel III (2001) proposed a clinically-based approach that establishes a diagnosis of metabolic syndrome (Mets), when an individual has 3 of 5 risk factors for cardiovascular disease.6 There appears to be considerable overlap in the clustering of cardiovascular disease mechanisms involved in Mets and OSA. Indeed, 5 recent studies have shown that OSA was significantly associated with Mets.7–11 However, 4 of the 5 were non-epidemiological studies, while subjects in the one epidemiological study were relatively obese for an Asian population.9 Another study has reported that obesity,12 and not OSA was responsible for metabolic abnormalities. Thus, it has not yet been established whether Mets is primarily determined by obesity or sleep apnea. In addition, although the prevalence of OSA in Mets subjects is not well understood,9 the converse (i.e., the prevalence of Mets in OSA subjects) has been investigated several times.7–11 We hypothesized that OSA would be an independent risk factor for Mets in a normal male population. We investigated the prevalence of sleep apnea in subjects with Mets in a Japanese male working urban city population (n = 275) whose body mass index (BMI) matched that of the general Japanese male population.13 In this study, we also looked at the prevalence of OSA in Mets subjects, as this is an area that has not been investigated extensively. Recently, in addition to obese subjects, it has been reported that Mets subjects have a shortened sleep duration which has a significant association with morbidity and mortality.14–19 In these studies, the sleep duration was measured by a sleep diary, rather than with an actigraph.20 The sleep duration in bed as measured by an actigraph has been shown to be compatible with the duration as measured by polysomnography.21 We also investigated weekly mean sleep duration by means of an actigraph.

Aim Obstructive sleep apnea (OSA) is a risk factor for cardiovascular diseases. Platelets play key roles in the development of atherothrombosis. Several studies assessing platelet activation in patients with OSA have been published; however, there have been only a few studies with a small number of patients with OSA investigating platelet aggregability, which evaluates platelet aggregation more directly than the platelet activation status. We aimed to investigate the effects of OSA and nasal continuous positive airway pressure (nCPAP) therapy, a well-established treatment for OSA, on platelet aggregability. Methods and results We examined 124 consecutive patients with snoring in whom the 3% oxygen desaturation index (3%ODI), a severity marker of OSA, and ADP- and collagen-induced platelet aggregability measured with the optical aggregometer were analyzed. ADP-induced platelet aggre-gability was increased more in patients with moderate-to-severe OSA (3%ODI>15) than in patients with non-to-mild OSA (p=0.029). In multiple linear models, 3%ODI significantly contributed to increased platelet aggregability induced by both ADP and collagen among 59 subjects with one or more risk factors for vascular diseases, such as smoking, hypertension, diabetes mellitus or hyperlipidemia. In 23 patients treated by nCPAP, collagen-induced platelet aggregability was ameliorated on Day 90, compared to at the baseline. Conclusion The severity of OSA significantly contributed to platelet aggregability, which was improved by nCPAP treatment partially at three months.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix (ECM) proteins, which lead to distorted lung architecture and function. Given that anti-inflammatory or immunosuppressive therapy currently used for IPF does not improve disease progression therapies targeted to blocking the mechanisms of fibrogenesis are needed. Although transforming growth factor-beta (TGF-beta) functions are crucial in fibrosis, antagonizing this pathway in bleomycin-induced pulmonary fibrosis, an animal model of IPF, does not prevent fibrosis completely, indicating an additional pathway also has a key role in fibrogenesis. Given that the loss of cytosolic phospholipase A(2) (cPLA(2)) suppresses bleomycin-induced pulmonary fibrosis, we examined the roles of prostaglandins using mice lacking each prostoaglandin receptor. Here we show that loss of prostaglandin F (PGF) receptor (FP) selectively attenuates pulmonary fibrosis while maintaining similar levels of alveolar inflammation and TGF-beta stimulation as compared to wild-type (WT) mice, and that FP deficiency and inhibition of TGF-beta signaling additively decrease fibrosis. Furthermore, PGF(2alpha) is abundant in bronchoalveolar lavage fluid (BALF) of subjects with IPF and stimulates proliferation and collagen production of lung fibroblasts via FP, independently of TGF-beta. These findings show that PGF(2alpha)-FP signaling facilitates pulmonary fibrosis independently of TGF-beta and suggests this signaling pathway as a therapeutic target for IPF.

This study investigated the consumption level, beverage preference and factors affecting alcohol intake by Japanese COPD patients. Three hundred patients diagnosed with COPD within the past four years were recruited from six hospitals in central Japan and interviewed. Of the 278 eligible participants (244 men and 34 women), 61.5% of male and 23.5% of female patients drank alcohol regularly on at least a monthly basis. The most preferred alcoholic beverage was beer (30.9%). The overall mean alcohol consumption was 29.7 (SD 42.5) g/day but drinkers had much higher mean intake of 52.2 (SD 44.8) g/day. Alcohol consumption level was significantly associated with the habit of adding soy sauce to food, gender and dyspnea but not the smoking status. The high alcohol consumption by COPD patients is alarming, with drinkers drinking well exceeded the government's recommended limit of 20 g daily. Alcohol control programs targeting male patients should be promoted to minimise the harm due to excessive drinking.

Background: Small airways play important roles in the pathophysiology of asthma. However, relationships between small airway involvement and health status and dyspnea have not been investigated. Objectives: It was the aim of this study to assess the relationships between proximal and peripheral airway functions and health status, dyspnea and disease control in patients with asthma, using impulse oscillometry (IOS). Methods: We performed IOS, spirometry and assessment of health status (Asthma Quality of Life Questionnaire and St. George’s Respiratory Questionnaire), dyspnea (Baseline Dyspnea Index) and disease control (Asthma Control Questionnaire) in 65 asthmatics and evaluated their relationships. Results: Peripheral airway function as evaluated by IOS [R5–R20 (the fall in resistance from 5 to 20 Hz) and X5 (reactance at 5 Hz)], in addition to the proximal airway index (R20), significantly correlated with health status, dyspnea and disease control. Multiple regression analyses revealed that peripheral airway function significantly contributes to these, independently of the proximal airway index. In contrast, forced expiratory volume in 1 s did not significantly contribute to health status or dyspnea. Conclusions: IOS correlated better with clinical symptoms and asthma control than spirometry in patients with asthma. Peripheral and proximal airway functions as assessed separately by IOS independently contribute to health status, dyspnea and disease control, indicating that peripheral airways also represent an important therapeutic target.

Three methods have been developed to measure health-related quality of life (HRQoL) expressed as a single value: the global rating scale, the total score obtained from disease-specific instruments, and the preference-based utility index. We compared these different single HRQoL measurements in patients with asthma and chronic obstructive pulmonary disease (COPD). We recruited 167 patients with asthma and 161 patients with COPD. The global rating HRQoL was assessed by the Hyland scale. The total HRQoL was assessed by the Living With Asthma Questionnaire in asthma and the St. George's Respiratory Questionnaire in COPD. The Quality of Well-being (QWB) scale was used for the utility measurement derived from the Medical Outcome Study Short-form 36. The inter-relationships between these three HRQoL values were weak to moderate in asthma and moderate in COPD. In asthma, the Hyland scale was weakly correlated with the total HRQoL (Spearman's rank correlation coefficients [Rs] = -0.20) and moderately with the QWB score (Rs = -0.43). In the stepwise multiple regression analyses, anxiety on the Hospital Anxiety and Depression scale and the dyspnea score tended to correlate more significantly with the single HRQoL values in both asthma and COPD than physiological measurements such as the forced expiratory volume in one second. The Hyland scale was less correlated with existing parameters (cumulative coefficient determination [R(2)] = 0.04) than the total HRQoL (cumulative R(2) = 0.47) and the QWB scale (cumulative R(2) = 0.49) in asthma. The single HRQoL values from the Hyland scale, the total HRQoL and the QWB scale evaluated different aspects of asthma and COPD. The psychological status and dyspnea contributed more significantly to the single HRQoL values in these two disorders than the physiological measurements. In asthma, the Hyland scale was especially different from the other single HRQoL scales and should be evaluated separately from the multi-item HRQoL assessments.

Background: It was previously reported that visual scores of the lung opacities were associated with lung function in patients with sarcoidosis. However, there are no reports on the evaluation of airway dimensions or lung density by computed tomography (CT) in sarcoidosis patients. Objectives: The aim of this study was to investigate whether airway dimensions and lung densities assessed by CT associate with pulmonary function in patients with sarcoidosis. Methods: CT scanning was performed in 43 sarcoidosis patients and lung densities were measured using in-house software. Means and standard deviations of lung density, kurtosis and skewness of lung density histograms were calculated. Tracheal area and airway wall area/total airway area (WA%) of the right apical bronchus were also measured. Pulmonary function tests were performed on the same day. Results: Increased standard deviation of lung density and decreased kurtosis and skewness of lung density histograms were all associated with decreased total lung capacity, vital capacity and diffusion capacity. Increased standard deviation of lung density was also associated with decreased percentages of forced expiratory volume in 1 s and peak expiratory flow (%PEF). There was a positive correlation between tracheal area corrected by body surface area and %PEF, and negative correlation between WA% and %PEF. Stepwise regression analysis showed that increased standard deviation of lung density and decreased tracheal area were independently associated with lower %PEF. Conclusions: Thus, in sarcoidosis, densitometric parameters reflect restrictive lung function impairment. In addition to parenchymal lesions, it is concluded that the luminal area of the central airways also affects PEF.

Background and aim: Obstructive sleep apnea (OSA) is a risk factor for cerebrovascular diseases. One cause for them is an occlusive arterial thrombus triggered by local platelet activation. Whether OSA is an independent risk factor for increased platelet aggregability is unclear. Methods: We enrolled 124 patients with snoring or daytime sleepiness in whom 3% oxygen desaturation index (3%ODI), a principal marker of the severity of intermittent hypoxia and reoxygenation (IHR), was measured. We studied ex vivo ADP- and collagen-induced aggregation of platelet-rich plasma using an optical aggregometer. The agonist concentration giving half maximal aggregation was defined as the platelet-aggregation threshold index (PATI) value. Therefore, the lower PATI value implicates the higher aggregability. In 23 patients who underwent nasal CPAP, platelet aggregability was followed until 90 days. Results: There was a significant difference in the PATI value for ADP-induced aggregation between 66 patients with non-to-mild OSA (3%ODI≤15) (1.04±0.07 μM, mean±SE) and 58 patients with moderate-to-severe OSA(3%ODI>15) (0.78±0.09 μM)(p=0.029). Multiple linear model revealed that 3%ODI strongly significantly contributed to the PATI values for ADP (p Conclusions: OSA patients had increased platelet aggregability. Severity of IHR more significantly contributed to platelet aggregation than total hypoxic time. Among OSA patients with conventional cardiovascular risk factors, the effects of IHR on the platelet aggregability was prominent. Nasal CPAP initially induced a transient hyperaggregable state of platelets, after which it continued to improve.

Rationale: Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. Objectives: To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. Methods: Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. Results: Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m2 or visceral fat area ≥100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation 2 = 15.1%, P

Summary Significant relationships between the psychological status and poor asthma outcomes are often reported. However, most of these studies are cross-sectional and none have evaluated how the psychological status progresses over time during the management of asthma patients. Therefore, we examined the longitudinal changes in the psychological status of asthma patients, and compared them with changes in other clinical measurements. Eighty-seven outpatients with stable asthma after 6 months of treatment were enrolled in this study. The psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS), the health status using the Asthma Quality of Life Questionnaire (AQLQ) and the St. George's Respiratory Questionnaire (SGRQ). The patient's pulmonary function, peak expiratory flow values and airway hyperresponsiveness were measured at entry and every year thereafter over a 5-year period. Using mixed effects models to estimate the slopes, the HADS anxiety and depression scores did not change significantly over time ( p =0.71 and 0.72, respectively). The changes in the HADS scores correlated noticeably with changes in the AQLQ and SGRQ scores, but not with changes in the physiological measurements. The baseline HADS anxiety and depression scores were significantly correlated to the subsequent annual changes in each measurement. The psychological status remained clinically stable over the 5-year study period in patients with stable asthma. Changes in the psychological status were significantly correlated to changes in the health status. The baseline HADS scores were a useful indicator in detecting patients who would show subsequent deterioration in their psychological status.

Summary Goals of effective management of patients with chronic obstructive pulmonary disease (COPD) include relieving their symptoms and improving their health status. We examined how such patient reported outcomes would change longitudinally in comparison to physiological outcomes in COPD. One hundred thirty-seven male outpatients with stable COPD were recruited for the study. The subjects health status was evaluated using the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ). Their dyspnoea using the modified Medical Research Council (MRC) scale and their psychological status using the Hospital Anxiety and Depression Scale (HADS) were assessed upon entry and every 6 months thereafter over a 5-year period. Pulmonary function and exercise capacity as evaluated by peak oxygen uptake \( V ˙ O 2 \) on progressive cycle ergometry were also followed over the same time. Using mixed effects models to estimate the slopes for the changes, scores on the SGRQ, the CRQ, the MRC and the HADS worsened in a statistically significant manner over time. However, changes only weakly correlated with changes in forced expiratory volume in 1s (FEV 1 ) and peak V ˙ O 2 . We demonstrated that although changes in pulmonary function and exercise capacity are well known in patients with COPD, patient reported outcomes such as health status, dyspnoea and psychological status also deteriorated significantly over time. In addition, deteriorations in patient reported outcomes only weakly correlated to changes in physiological indices. To capture the overall deterioration of COPD from the subjective viewpoints of the patients, patient reported outcomes should be followed separately from physiological outcomes.

Although exercise capacity is an important outcome measure in patients with COPD, its longitudinal course has not been analyzed in comparison to the change in pulmonary function.To examine how exercise capacity would deteriorate over time in patients with COPD, and what factors would contribute to it.A total of 137 male outpatients with moderate-to-very-severe COPD were examined. The average age was 69.0 +/- 6.6 years (+/- SD), and the mean postbronchodilator FEV(1) was 45.9 +/- 15.4% predicted. Progressive cycle ergometry and pulmonary function testing were performed at entry, and every 6 months thereafter over 5 years. Due to the presence of missing data, a mixed-effect model analysis was then used to estimate the longitudinal changes in various clinical parameters.Peak oxygen uptake (Vo(2)), peak minute ventilation (Ve), and peak tidal volume (Vt) during exercise declined significantly over time (p0.0001), which was no less rapid than the deterioration in FEV(1). The mean decline rates for peak Vo(2) were 32 +/- 60 mL/min/yr and 0.5 +/- 1.0 mL/min/kg/yr. Multiple regression analysis revealed that the changes in peak Ve, peak Vt, and peak respiratory rates were significant predictors for the change in peak Vo(2).We demonstrated clear evidence of measurable and progressive deterioration in exercise capacity in COPD patients, which was no less rapid than the decline in airflow limitation. Dynamic ventilatory constraints during exercise also deteriorated over time, which most significantly contributed to this exercise capacity deterioration. In addition to pulmonary function, the longitudinal follow-up of exercise capacity is important not to miss the overall deterioration in COPD.

Long-term changes in health status have been less evaluated in patients with chronic obstructive pulmonary disease (COPD), in comparison to the changes in forced expiratory volume in 1 s (FEV1). Accordingly, we examined the clinical course of health status as well as pulmonary function in COPD patients, and investigated the relationship between the change in health status and the change in pulmonary function in a 3-year longitudinal study involving 224 patients with COPD. Health status using the Chronic Respiratory Disease Questionnaire (CRQ) and pulmonary function were measured at baseline and every six months over three years. We used the random effects model for the slopes to estimate the longitudinal changes. A total of 147 patients completed the 3-year study. The dyspnoea, fatigue, and emotional function domains of the CRQ declined slowly but significantly over 3 years (p = 0.001, 0.003, and 0.004, respectively) with a mean decline rate of 0.08/year. This means that it would take about 6 years to reach the minimal important change of 0.5 on the CRQ. The mean decline in post-bronchodilator FEV1 was 60 ml/year. None of the changes in any of the domains of the CRQ were significantly correlated with the changes in pulmonary function. We have found that, in comparison to the decline in pulmonary function, health status evaluated by the CRQ declined significantly but very slowly in three of four domains over three years in patients with COPD. Furthermore, we have demonstrated that there was no significant relationship between the change in health status and the change in pulmonary function.

Study objectives To assess the optimal cutoff level of breath CO concentration to distinguish actual smokers from nonsmokers among patients with asthma and COPD. Setting Kyoto University Hospital outpatient clinic. Subjects and methods Three hundred thirty-one consecutive outpatients (161 with asthma and 170 with COPD) were examined cross-sectionally by self-reported smoking status, breath CO monitoring, and serum cotinine concentration. Actual smoking status was verified by serum cotinine concentration. Results Mean serum cotinine concentrations of never smokers, former smokers, and current smokers with asthma were 6.0 ± 5.2 ng/mL, 12.1 ± 25.0 ng/mL, and 198.3 ± 181.7 ng/mL, respectively (± SD). Mean serum cotinine concentrations of former smokers and current smokers with COPD were 23.2 ± 69.2 ng/mL and 191.1 ± 109.8 ng/mL, respectively. Mean breath CO levels of never smokers, former smokers, and current smokers with asthma were 6.1 ± 2.4 ppm, 7.7 ± 3.2 ppm, and 19.9 ± 17.3 ppm, respectively. Mean breath CO levels of former smokers and current smokers with COPD were 7.7 ± 4.3 ppm and 13.5 ± 6.5 ppm, respectively. The optimal cutoff level of breath CO to discriminate between actual smokers and nonsmokers was 10 ppm in patients with asthma and 11 ppm in patients with COPD, giving 85.0% and 73.1% sensitivity, and 85.8% and 84.7% specificity, respectively. Conclusion The optimal cutoff level of breath CO to assess actual smoking status was 10 ppm in patients with stable asthma and 11 ppm in patients with stable COPD. In patients with asthma and COPD, breath CO levels were potentially influenced by underlying airway inflammation, suggesting misclassification in the assessment of smoking status by breath CO.

Generic health status has been recommended to be measured separately from disease-specific health status, because they can yield complementary information. In particular, generic health status can provide comprehensive health ratings across various disorders. However, the weakness with generic measures is that they may be less responsive to clinical changes than disease-specific ones. Therefore, when using generic health status as an endpoint in clinical trials, the instrument to be used is a problem with respect to responsiveness. In the present study, we investigated and compared the responsiveness of health status measures during asthma treatment using three different generic instruments: the Medical Outcomes Study Short Form 36-items Health Survey (SF-36), the Nottingham Health Profile (NHP) and the EQ5D (EuroQoL), as well as one disease-specific instrument, the Asthma Quality of Life Questionnaire (AQLQ). Fifty-four new patients with asthma who consulted our clinic were recruited. The health status measurements were performed on the initial visit, and at 3 and 6 months. All subscales of the SF-36 showed a significant improvement during the first 6 months. Each dimension of the EQ5D showed stronger ceiling effects than the SF-36. With respect to the responsiveness indices, the SF-36 was regarded as more responsive than the NHP or EQ5D utility. The changes in the SF-36 had a weak to moderate correlation with the changes in the AQLQ. In conclusion, the SF-36 had a higher responsiveness for asthma as a generic measure than the NHP or EQ5D, and evaluated different aspects from the AQLQ. The SF-36 can be used effectively in asthma clinical trials.

Purpose: The purpose of this study was to make comparisons between different types of exercise tests used in chronic obstructive pulmonary disease (COPD) to better interpret the results and to select the most suitable testing procedure. Therefore, we evaluated the relationship between exercise capacity and other clinical measures and their relative contributions to exercise capacity in patients with COPD. Method: We studied 36 patients with stable COPD. All patients underwent baseline pulmonary function testing. Dyspnea during activities of daily living was assessed with the Oxygen Cost Diagram (OCD). The Hospital Anxiety and Depression Scale and the St George's Respiratory Questionnaire were used to assess psychologic status and health-related quality of life, respectively. All patients performed the 6-minute walking test, progressive cycle ergometry, and the cycle endurance test. Results: Each exercise capacity result correlated significantly with pulmonary function, the OCD, and the Activity and Total scores of the St George's Respiratory Questionnaire. Multiple regression analyses revealed that the OCD was an important predictor of exercise capacity, especially for the walking test. Diffusing capacity was also a significant predictor on progressive cycle ergometry. Body mass index was the most significant predictor of the endurance time. Conclusion: The 3 different exercise tests had similar characteristics in relation to pulmonary function, dyspnea, and health-related quality of life in patients with COPD. However, some differences were found in the aspects they evaluated. (Heart Lung® 2002;31:374-81.)

In this study, we analyzed the relationships of exercise capacity by the percentage of predicted FEV1 (4). Celli proposed a and health status to mortality in patients with chronic obstructive systemic evaluation of COPD patients and stressed that there pulmonary disease (COPD). We recruited 150 male outpatients with is a need to seek candidates for multidimensional disease stable COPD with a mean postbronchodilator FEV1 at 47.4% of staging (5). Exercise capacity and health status may also be predicted. Their pulmonary function, progressive cycle ergometry, important clinical indices to evaluate disease impairment in and health status using the Chronic Respiratory Disease Question- addition to FEV1. naire, the St. George’s Respiratory Questionnaire (SGRQ), and the Although airflow limitation is the most obvious manifestaBreathing Problems Questionnaire were measured at entry. Among tion of COPD, COPD has other extrapulmonary features 144 patients who were available for the 5-year follow-up, 31 had and should be regarded as a systemic disorder (6). This multidied. Univariate Cox proportional hazards analysis revealed that pathophysiologic aspect of COPD can influence exercise cathe SGRQ total score and the Breathing Problems Questionnaire pacity (7) and health status (8). Therefore, we hypothesized were significantly correlated with mortality; however, with the that they could predict mortality in COPD. In this study, Chronic Respiratory Disease Questionnaire, the total score was not we investigated the relationships between various clinical significantly correlated. Multivariate Cox proportional hazards anal- parameters, including exercise capacity and health status, and ysis revealed that the peak oxygen uptake and the SGRQ total score mortality in patients with COPD after 5 years. In addition, were both predictive of mortality, independent of FEV1 and age. we examined which clinical parameter was the most imporStepwise Cox proportional hazards analysis revealed that the peak tant when regarding mortality as the reference outcome. oxygen uptake was the most significant predictor of mortality. We found that exercise capacity and health status were significantly correlated with mortality, although different health status measures METHODS had different abilities to predict mortality. These results will have Patients a potentially great impact on the multidimensional evaluation of disease severity in COPD.

Background: Disease-specific health status measures are characterized by higher responsiveness than generic measures and may be preferred in clinical trials. However, comparisons of responsiveness between various disease-specific measures have rarely been performed in asthma studies. Study objective: We investigated and compared the responsiveness of health status scores in asthmatic patients during treatment using three different disease-specific measures: the Juniper Asthma Quality of Life Questionnaire (AQLQ), the Living with Asthma Questionnaire (LWAQ), and the Airways Questionnaire 20 (AQ20). Methods: We attempted to follow up 170 patients with newly diagnosed asthma over a 6-month period. Patients underwent treatment with inhaled corticosteroids in accordance with the guideline. A health status evaluation using three disease-specific measures, and pulmonary function tests were performed on the initial visit, and at 3 months and 6 months. The effect size and the standardized response mean were used as responsiveness indexes. Results: A total of 109 patients completed the 6-month follow-up and were then analyzed. All health status scores and FEV1 measures improved during the first 3 months (p < 0.001). The total of the AQLQ scores showed high responsiveness indexes ranging from 1.28 to 1.46 between baseline and 3 months, and baseline and 6 months. Spearman correlation coefficients were smaller between the change in FEV1 and the change in the LWAQ. Although the AQ20 also demonstrated high responsiveness, a ceiling effect was indicated. Conclusions: The AQLQ was the most responsive measure during asthma treatment. The relationship between the change in airflow limitation and the change in the LWAQ was weaker compared to the AQLQ and the AQ20. Although the AQ20 was also responsive and its simplicity is favorable, the ceiling effect should be considered when using it. (CHEST 2002; 122:1228 –1233)

FEV(1) is regarded as the most significant correlate of survival in COPD and is used as a measure of disease severity in the staging of COPD. Recently, however, the categorization of patients with COPD on the basis of the level of dyspnea has similarly been reported to be useful in the prediction of health-related quality of life and improvement in exercise performance after pulmonary rehabilitation.We compared the effects of the level of dyspnea and disease severity, as evaluated by airway obstruction, on the 5-year survival rate of patients with COPD.A total of 227 patients with COPD were enrolled in a 5-year, prospective, multicenter study in the Kansai area of Japan, involving 20 divisions of respiratory medicine from various university and city hospitals.After 5 years, 183 patients were available for the follow-up examination (follow-up rate, 81%). The 5-year cumulative survival rate among patients with COPD was 73%. The effect of disease staging, based on the American Thoracic Society (ATS) guideline as evaluated by the percentage of predicted FEV(1), on the 5-year survival rate was not significant (p = 0.08). However, the level of dyspnea was significantly correlated to the 5-year survival rate (p0.001). The Cox proportional hazards model revealed that the level of dyspnea had a more significant effect on survival than disease severity based on FEV(1).The categorization of patients with COPD on the basis of the level of dyspnea was more discriminating than staging of disease severity using the ATS guideline with respect to 5-year survival. Dyspnea should be included as one of the variables, in addition to airway obstruction, for evaluating patients with COPD in terms of mortality.

In the management of patients with asthma, peak expiratory flow (PEF) monitoring is used and based on the individual best PEF or the predicted PEE Recent international guidelines have recommended the use of the best PEF rather than the predicted PEF as an index, although there is little evidence to support which index is more appropriate. Therefore, we investigated the relationship between the best PEF and the predicted PEF in 166 consecutive asthmatic patients to see which value would be the better basis for their PEF monitoring. All eligible patients had undergone treatment for their asthma for over 6 months and were asked to measure their PEF four times a day. The best PEF was defined as the maximal PEF achieved at any time from all previous measurements. The predicted PEF was calculated based on a report on the standard PEF in normal Japanese subjects. The mean best PEF was significantly higher than the mean predicted PEF (p < 0.001). There was a strong correlation between the best PEF and the predicted PEF (r = 0.77, p < 0.001). However, in 72 patients (43%) the ratio of the best PEF to the predicted PEF was over 110%, and in 20 patients (12%) the ratio was lower than 90%. The best PEF was higher than the predicted PEF in 76 patients (46%) and lower in 22 patients (13%) by more than 50 L/min. These results suggest that when the predicted PEF was used as the index, pulmonary function was either underestimated or overestimated in over half of these patients. Therefore, the best PEF may be the better index for the management of patients with asthma.

The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance. Thirty-eight males with stable chronic obstructive pulmonary disease (COPD) (FEV 1 5 40.8 6 16.5% predicted; mean 6 SD) completed randomized, double-blind, placebo-controlled, crossover studies for each exercise test. The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 m g or placebo. The patients performed 6-min walking tests (6MWT) on Days 1 and 2, progressive cycle ergometry (PCE) on Days 3 and 4, and cycle endurance tests at 80% of the maximal workload of PCE on Days 5 and 6. Spirometry was conducted before and at 45 and 90 min after the inhalation. Oxitropium bromide significantly increased FEV 1 as compared with placebo. Oxitropium bromide increased the endurance time significantly, by 19% (p , 0.001), and caused a small but significant increase in the 6-min walking distance by 1% (p , 0.05), but induced no significant increase in maximal oxygen consumption ( O 2 max) in PCE. The responses in these three exercise tests were different, and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD. An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance. Patients with chronic obstructive pulmonary disease (COPD) complain of exertional breathlessness and exercise intolerance, mainly due to reduced ventilatory capacity and impaired gas exchange. Inhaled anticholinergic agents are recommended as the first-line drugs to relieve these patients’ symptoms and to improve their airflow limitation (1, 2). Although the bronchodilating effects of these drugs in COPD have been established (3, 4), there is sometimes controversy about whether anticholinergic agents affect exercise performance (5‐10). The effects of anticholinergic bronchodilators may depend on the type of exercise test performed. In investigating the effects of bronchodilators on exercise performance in patients with COPD, a walking test and progressive cycle ergometry (PCE) are often used (5‐10). However, in assessing the effects of pulmonary rehabilitation, endurance tests are sometimes used because measures of endurance may be responsive to training. An effective pulmonary rehabilitation program usually results in an improvement in exercise endurance, but little or no change in maximal exercise capacity (11). Recently, O’Donnell and coworkers reported that after bronchodilator therapy, exercise time was a reliable measure of exercise enV ·

Study objectives: To compare categorizations of the level of dyspnea with the staging of disease severity as defined by the FEV1 in representing how the health-related quality of life (HRQOL) is distributed in patients with COPD. Design: Cross-sectional study. Setting: Outpatient clinic at the respiratory department of a university hospital. Patients: A total of 194 consecutive male patients with stable, mild-to-severe COPD. Measurements: The score distributions for the components of the St. George’s respiratory questionnaire (SGRQ) were used as disease-specific HRQOL measures, and the scores from the Medical Outcomes Study Short Form 36-item questionnaire (SF-36) were used as generic HRQOL measures. These scores were stratified according to the level of dyspnea, as defined by the Medical Research Council (MRC) dyspnea scale, and the stage of disease severity, as defined by the American Thoracic Society (ATS). Differences in the HRQOL scores among the subgroups were compared by an analysis of variance (ANOVA). Multiple pairwise comparisons were made with Fisher’s least significant difference (LSD) method, with the overall a-level set at 0.05. Results: In those groups classified according to the level of dyspnea, significant differences were observed for the scores on the SGRQ and SF-36 (ANOVA, p < 0.05). The scores for activity and impact, and the total scores of the SGRQ and all scales, except for bodily pain and general health on the SF-36, were significantly worse for patients with severe dyspnea (MRC scale grades, 3, 4, and 5, respectively) than for those with moderate dyspnea (MRC grade level, 2; Fisher’s LSD method, p < 0.05). Significant differences were recognized among the different stages of disease severity with respect to the scores from all scales of the SF-36, except for bodily pain, and all scores from the SGRQ (ANOVA, p < 0.05). However, differences in the scores on the SGRQ and SF-36 between patients with ATS stage II disease (FEV1, 35 to 49% predicted) and stage III disease (FEV1, < 35% predicted) were not statistically significant. Conclusions: Using the SGRQ and SF-36, the HRQOL of patients with COPD was more clearly separated by the level of dyspnea than by the ATS disease staging. In addition to the ATS disease staging, categorizations based on the level of dyspnea may be useful to clinicians in terms of the HRQOL of COPD patients. (CHEST 1999; 116:1632‐1637)