Abstract: Abstract Background : Streptococcus pneumoniae is one of the most common bacteria identified 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 first 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 identified, 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.
Abstract: Background and Objective The endurance time has been reported to be the most sensitive measure of improved exercise capacity in response to a variety of interventions for COPD. The aim of the present study was to determine whether the improvements in quadriceps force and measures obtained from a symptom-limited maximal test contributed to the improvements in endurance time following pulmonary rehabilitation. Methods Fifty-seven consecutive COPD subjects completed a 10-week pulmonary rehabilitation program. The subjects completed a symptom-limited incremental cycle ergometry test and a constant work rate test before and after pulmonary rehabilitation. Peripheral and respiratory muscle strength was also measured. The relationships between the change in endurance time and the changes obtained from the incremental test and muscle strength test were investigated. Results The endurance time showed the greatest improvement among the exercise capacity indices. The changes in endurance time were significantly correlated to changes in quadriceps force, peak work rate, anaerobic threshold and work efficiency on the incremental load test. In the multiple stepwise regression analysis, changes in quadriceps force and work efficiency measured on the maximal exercise test were selected. Conclusion These findings suggest that the improvements in endurance time after pulmonary rehabilitation may be explained by increased quadriceps force and improvements in peak work rate and work efficiency.
Abstract: 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.
Abstract: Background: Systematic case identification has been proposed as a strategy to improve diagnosis rates and to enable the early detection of subjects with COPD. We hypothesized that case identification could be possible using the handheld spirometer Hi-Checker(TM). Aim: To determine how to modify the FEV(1)/FEV(6) values obtained using the Hi-Checker( TM) to screen for cases with airflow limitation. Methods: Spirometry was performed with both an electronic desktop spirometer and with the Hi-Checker(TM) in 312 male subjects. Results: The average FEV(1) (mean ± SD) measured using a conventional spirometer and the Hi-Checker(TM) was 2.99 ± 0.56L and 3.07 ± 0.57L, respectively. These results were significantly different (P<0.001, paired t-test for both). This difference of -0.08 ± 0.13L (95% confidence interval: -0.094-0.066L) was normally distributed, and thought to be random. Statistically significant correlations were found for all measurements between the spirometer and the Hi-Checker(TM); the Pearson's correlation coefficient (R) between the FEV(1)/FVC and FEV(1)/FEV(6) values was 0.881. If one defines a FEV(1/)FVC smaller than 0.7 measured by the spirometer as airflow limitation, then a FEV(1)/FEV(6) smaller than 0.746 measured by the Hi-Checker(TM) best matches this definition, and Cohen's kappa coefficient was 0.672. Conclusion: Although the Hi-Checker (TM) estimates resembled those from conventional spirometry, it should be emphasized that the two methods did not produce identical results due to random measurement error. Although one must be careful about overinterpreting these results, since the Hi-Checker (TM) is small and inexpensive, it could make a significant contribution in facilitating the case selection of patients with airflow limitation.
Abstract: Randomized controlled trials, evidence-based medicine, clinical guidelines, and total quality management are some of the approaches used to render science-based health care services. The clinical pathway for hospitalized patients suffering from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly established, although a clinical pathway is an integral part of total quality management.
Abstract: Emphysematous change as assessed by CT imaging has been reported to correlate with COPD prognostic factors such as FEV(1) and diffusing capacity of the lung for carbon monoxide (Dlco). However, few studies have assessed the relationship between CT scan assessment and COPD mortality from mild to severe stages of the disease. In this study, we analyzed this relationship in patients with various stages of COPD.
Abstract: The Japanese diet is high in soy products and fish. A case-control study was conducted in Japan to investigate the relationship between dietary intake of isoflavones and fatty acids and lung function, breathlessness and chronic obstructive pulmonary disease (COPD). A total of 278 referred patients aged 50-75 years with COPD diagnosed within the past 4 years, and 340 community-based controls were assessed for respiratory symptoms and undertook spirometric measurements of lung function. A validated food frequency questionnaire was administered face-to-face to obtain information on habitual food consumption. Dietary intakes of isoflavones and fatty acids were derived from the Japanese food composition tables. The COPD patients had significantly lower habitual intakes of isoflavones (genistein and daidzein) and polyunsaturated fatty acids (PUFA; both omega-3 and omega-6) than control subjects. Lung function measures were found to be positively associated with isoflavones and PUFA intake. Substantial reductions in prevalence of COPD and breathlessness were observed for isoflavones, the respective adjusted odds ratio being 0.36 (95% confidence interval 0.19-0.68) and 0.60 (95% confidence interval 0.33-1.10) for the highest versus lowest levels of total isoflavone intake. The corresponding tests for linear trend were significant. High intakes of PUFA and omega-6 fatty acids (derived from foods excluding oils and fats as seasonings) also appeared to reduce the risks of COPD and breathlessness symptom, but no evidence of association was found for other types of fatty acids. The study provided evidence of possible protective effect of traditional Japanese diet against tobacco carcinogens.
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory disorders involving obstructive airway defects. There have been many discussions on their similarities and differences. Although airflow limitation expressed as forced expiratory volume in one second (FEV(1)) has been considered to be the main diagnostic assessment in both diseases, it does not reflect the functional impairment imparted to the patients by these diseases. Therefore, multidimensional approaches using multiple measurements in assessing disease control or severity have been recommended, and multiple endpoints in addition to FEV(1) have been set recently in clinical trials so as not to miss the overall effects. In particular, as improving symptoms and health status as well as pulmonary function are important goals in the management of asthma and COPD, some patient-reported measurements such as health-related quality of life or dyspnea should be included. Nonetheless, there have been few reviews on the long-term clinical course comparing asthma and COPD as predicted by measurements other than airflow limitation. Here, we therefore analyzed and compared longitudinal changes in both physiological measurements and patient-reported measurements in asthma and COPD. Although both diseases showed similar long-term progressive airflow limitation similarly despite guideline-based therapies, disease progression was different in asthma and COPD. In asthma, patient-reported assessments of health status, disability and psychological status remained clinically stable over time, in contrast to the significant deterioration of these parameters in COPD. Thus, because a single measurement of airflow limitation is insufficient to monitor these diseases, multidimensional analyses are important not only for disease control but also for understanding disease progression in asthma and COPD.
Abstract: To investigate the relationship between soy consumption, COPD risk and the prevalence of respiratory symptoms, a case-control study was conducted in Japan.
Abstract: To investigate the relationship between vegetable and fruit consumption and the risk of chronic obstructive pulmonary disease (COPD), a case-control study was conducted in central Japan in 2006.
Abstract: Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD). The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations.
Abstract: In Japan, most cases of malignant lymphoma arising in the thorax are pyothorax-associated lymphoma, which develops in patients who have undergone artificial pneumothorax, used in the past as surgical therapy for pulmonary tuberculosis. Pyothorax-associated lymphoma consist mostly of diffuse large B-cell lymphoma and have a strong association with EBV. Herein is reported the case of a diffuse large B-cell lymphoma arising in the left thoracic wall after left lung resection for squamous cell carcinoma and chest wall reconstruction with polyethylene terephthalate (PET) surgical mesh. The tumor was found 20 years after the operation and was confined to the chest wall adjacent to the PET mesh. The patient did not have a clinical history of pyothorax after surgery. The lymphoma cells were of the large cell type and were positive for CD20, EBV-encoded small RNA--in situ hybridization, LMP-1 and EBNA-2. The present case demonstrates that EBV-related B-cell lymphoma can occur after surgery other than artificial pneumothorax. In the present case, long-standing chronic inflammation induced by PET mesh may have been associated with the development of lymphoma.
Abstract: This study investigated urinary incontinence in men with chronic obstructive pulmonary disease (COPD). A total of 244 community-dwelling men (mean age 66.5 years) diagnosed with COPD within the past 4 years were recruited from six hospital outpatient departments in central Japan. The prevalence of urinary incontinence was 10% according to the International Consultation on Incontinence criterion. Urine leakage among the 24 incontinent men was typically a small amount (75%) and occurred once a week or less often (58%). Fifteen (63%) of them reported urge incontinence while only two men experienced stress incontinence. On average they had urine leakage for 2.5 (SD 2.3) years and the majority (n = 19, 79%) developed the condition after diagnosis of COPD. The finding of higher prevalence of urge incontinence challenges the conventional view that COPD is associated with stress incontinence due to high pressure coughs.
Abstract: 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.
Abstract: Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.
Abstract: 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.
Abstract: 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.
Abstract: 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 (VO2) 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 (VO2). 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.
Abstract: Japan appears to be one of the healthiest nations. However, each step of healthcare services is not excellent while macroscopic outcomes are exceptional. Globalization is also key concept in Japanese respiratory healthcare services. As international communication between physicians become more common, the reality that various gaps in respiratory healthcare services still remain in place is becoming clearer. Now, clinicians are paying attention to global sources of information. Respiratory medicine will also change from experience-based medicine to evidence-based science.
Abstract: Dyspnoea measurements in chronic obstructive pulmonary disease (COPD) can be broadly divided into two categories: those that assess breathlessness during exercise, and those that assess breathlessness during daily activities. We investigated the relationships between dyspnoea at the end of exercise and during daily activities with clinical measurements and mortality in COPD patients. We examined 143 male outpatients with moderate to very severe COPD. The peak Borg score at the end of progressive cycle ergometry was used for the assessment of peak dyspnoea rating during exercise, and the Baseline Dyspnea Index (BDI) score was used for dyspnoea with activities of daily living. Relationships between these dyspnoea ratings with other clinical measurements of pulmonary function, exercise indices, health status and psychological status were then investigated. In addition, their relationship with the 5-year mortality of COPD patients was also analyzed to examine their predictive ability. Although the BDI score was significantly correlated with airflow limitation, diffusing capacity, exercise indices, health status and psychological status, the Borg score at the end of exercise had non-existent or only weak correlations with them. The BDI score was strongly significantly correlated with mortality, whereas the Borg score was not. Dyspnoea during daily activities was more significantly correlated with objective and subjective measurements of COPD than dyspnoea at the end of exercise. In addition, the former was more predictive of mortality. Dyspnoea with activities of daily living is considered to be a better measurement for evaluating the disease severity of COPD than peak dyspnoea during exercise.
Abstract: BACKGROUND: 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. PURPOSES: To examine how exercise capacity would deteriorate over time in patients with COPD, and what factors would contribute to it. METHODS: 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. RESULTS: Peak oxygen uptake (Vo(2)), peak minute ventilation (Ve), and peak tidal volume (Vt) during exercise declined significantly over time (p < 0.0001), 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). CONCLUSION: 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.
Abstract: The prognosis of patients with idiopathic pulmonary fibrosis (IPF) is generally considered to be poor. As the disease progresses, patients invariably become severely limited in their activities. Therefore, evaluating the health-related quality of life (HRQoL) in IPF patients is considered to be important. However, there have been few studies of this kind to date. We applied the St. George's Respiratory Questionnaire (SGRQ) to 41 consecutive IPF patients and examined various physiological variables to identify factors that were correlated with the HRQoL. Total lung capacity, transfer factor, arterial partial pressure of oxygen at rest, the lowest oxygen saturation during exercise test, and the baseline dyspnoea index (BDI) score were significantly correlated with the total SGRQ score. A similar tendency was observed in each component. Conversely, peak oxygen uptake, known as one of the important factors that determines HRQoL in chronic obstructive pulmonary disease (COPD), did not correlate with any SGRQ scores. In stepwise multiple regression analysis, the BDI score was selected as the only factor significantly contributing to the total SGRQ score. Dyspnoea was the most important factor determining HRQoL in IPF. The types of other variables that correlated with the HRQoL in IPF patients were different from those in COPD.
Abstract: BACKGROUND AND OBJECTIVE: Although improving health status is one important aim in managing asthmatic patients, few studies have evaluated their health status longitudinally. Therefore, we examined longitudinal changes in health status of asthma patients, and compared them with changes in physiological measures. METHODS: Eighty-seven outpatients with stable asthma after 6 months of treatment were recruited. Health status using the Asthma Quality of Life Questionnaire (AQLQ) and the St. George's Respiratory Questionnaire (SGRQ), pulmonary function, peak expiratory flow (PEF) values, and airway hyperresponsiveness (AHR) were evaluated at entry and every year over a 5-year period. RESULTS: Using mixed effects models to estimate the slopes, the overall AQLQ score declined statistically at a mean rate of 0.06 units/year (P=.0091). However, this decline did not reach a clinically significant level at 5 years. The total SGRQ score did not change significantly (P=.54). Although the forced expiratory volume in 1 sec declined at a mean rate of 53 mL/year, the PEF variability and AHR improved significantly. CONCLUSION: Health status was clinically stable over the 5-year study period in patients with asthma, which contrasted with the changes in the physiological outcome measures. As a patient centered outcome measure, health status should be followed separately.
Abstract: OBJECTIVES: Despite high smoking rates, few prevalence studies of COPD have been performed in Asia. The Nippon COPD Epidemiology (NICE) Study used spirometry to measure prevalence of airflow limitation in Japanese adults. METHODOLOGY: Clinical, spirometric, and risk factor exposure data were collected on 2343 subjects aged > or = 40 years who were demographically similar to the Japanese population. Airflow limitation was defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC < 70%). RESULTS: Prevalence of airflow limitation was 10.9%. Based upon GOLD severity criteria, 56% of these cases were found to be mild, 38% moderate, 5% severe, and 1% very severe. Airflow limitation was significantly more prevalent in males than females (16.4% vs. 5.0%; P < 0.001), in male ever-smokers than female ever-smokers (17.1% vs. 7.5%; P < 0.001), and in older subjects (3.5% in 40-49 years olds vs. 24.4% in those > 70 years; P < 0.001). Of note, airflow limitation was also found in 5.8% of non-smokers and 4.6% of those younger than age 60 years. Only 9.4% of cases with airflow limitation reported a previous diagnosis of COPD. CONCLUSIONS: Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.
Abstract: Endurance time on submaximal exercise tests is a sensitive measure in detecting changes after medical intervention and is used as an outcome in clinical trials, although there has been little discussion regarding the appropriate intensity. Therefore, we investigated whether there were differences in exercise responses between endurance tests at high versus moderate intensity, and analyzed which test was more appropriate. Thirty-seven patients with chronic obstructive pulmonary disease participated in the study. They performed cycle endurance tests at high and moderate submaximal workloads representing 80% and 60% of the maximum work rate reached on progressive cycle ergometry, respectively. Each type of exercise test was performed after inhaling salbutamol 400 microg, ipratropium bromide 80 microg or an identical placebo. Endurance time on the 80% endurance test was much shorter than on the 60% endurance test. The coefficients of variation for the endurance time were lower on the 80% test. Statistically significant improvements in the endurance time after bronchodilators in comparison to placebo were found only on the 80% test. When using the endurance time as an outcome, the high intensity endurance test is preferable to the moderate intensity endurance test, as the high intensity test demonstrated shorter exercise time, less variability and higher sensitivity.
Abstract: The aim of this study is to evaluate the discriminative properties of the Multidimensional Quality of Life Questionnaire for HIV infection (MQoL-HIV) and to determine those factors contributing to the health-related quality of life (HRQoL) of HIV-1 infected persons living in Japan. The MQoL-HIV, the Nottingham Health Profile (NHP) as a generic instrument, and the Center for Epidemiologic Studies-Depression Scale (CES-D) as a psychological measure were administered in 375 patients as a multiple-centre study. The score distribution of the MQoL-HIV showed a unimodal distribution. The Cronbach's alpha coefficient scored more than 0.7 in seven out of 10 domains, but was low in both the physical functioning and sexual functioning domains. There was a strong correlation between the CES-D and MQoL-HIV index scores (R-0.73). Relatively high coefficient values were found between psychiatric and nervous symptoms and the index score (R=-0.60). In total, the MQoL-HIV may possess discriminative properties.
Abstract: Simple and concise measures for health status are desirable in clinical practice. The Asthma Bother Profile (ABP), which consists of 23 items, has been developed to assess how much asthma bothers patients. The Airways Questionnaire 20 (AQ20) is a simple instrument which consists of 20 items. The purpose of this study was to investigate how the ABP and AQ20 evaluate the health status of patients with asthma. A total of 166 patients with chronic asthma (age: 48 +/- 16 yr, 77 males) completed pulmonary function testing, measurement of airway hyperresponsiveness, dyspnea rating, assessments of their anxiety and depression (HADS; Hospital Anxiety and Depression Scale), and assessments of their health status. The health status was assessed using the ABP, AQ20, the short-form 36 health survey questionnaire (SF-36), the Living With Asthma Questionnaire (LWAQ) and the Asthma Quality of Life Questionnaire (AQLQ). The Japanese version of the ABP included only 15 'bother' items out of the original 23 items due to cultural differences. The scores on the ABP were widely distributed, whereas the scores on the AQ20 were skewed towards the milder end of the scale. The ABP had a strong correlation with the Avoidance and Distress constructs on the LWAQ, and Anxiety and Depression on the HADS (Rs = 0.56 to approximately 0.79), and its strongest correlation with the General Health (Rs = -0.64) scale among the 8 subscales on the SF-36. The AQ20 had a less significant correlation with the LWAQ, AQLQ, and SF-36 than the ABP. The ABP and AQ20 were short and simple to complete, and both measures could easily be used in clinical practice. The ABP can evaluate patients more specifically with respect to distress and bother than the AQ20.
Abstract: The purpose of the present study was to investigate the responsiveness of the Short Form-36 (SF-36) in patients with chronic obstructive pulmonary disease (COPD) and asthma. We studied patients with COPD and asthma who attended our outpatient clinic. In the first cross-sectional study, we compared the differences in the SF-36 scores between pretreatment patients (152 with COPD and 174 with asthma) who visited the clinic for the first time and in-treatment patients (123 with COPD and 151 with asthma) who had received treatment for > 6 months. The differences in each scale of the SF-36 ranged from 6.9 to 14.4 in COPD patients and from 7.0 to 28.3 in asthma patients. In the second longitudinal study, patients who visited for the first time were enrolled, and the initial, and, 3-, 6-, and 12-month evaluations of the SF-36 were studied. A total of 136 COPD patients and 136 asthma patients were enrolled consecutively, and 100 patients with COPD and 66 patients with asthma completed the year-long examinations. In COPD patients, except for bodily pain, the scores in all scales of the SF-36 improved significantly during the first 3 or 6 months. In patients with asthma, all scale scores of the SF-36 improved significantly during the first 3 months. Maximal changes in the SF-36 scores were observed at 6 or 12 months. Longitudinal maximal changes in each scale approached or exceeded the possible maximal changes, which were derived from the differences in the scores between pretreatment patients and in-treatment patients in the first cross-sectional study. Improvements in the SF-36 scores showed moderate to strong negative correlations with their baseline scores in patients with COPD and asthma. In conclusion, the SF-36 shows sufficient responsiveness in the assessment of the health status of patients with COPD and asthma, but these responses are strongly influenced by their baseline values.
Abstract: 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.
Abstract: OBJECTIVE: To adapt the Nottingham Health Profile (NHP) for Japanese and to describe the results of the assessment of its psychometric properties. METHODS: Assessments included test-retest reliability over approximately a 2-week interval, internal consistency and construct validity in 133 patients with COPD. RESULTS: The distribution of scores indicated that most of the NHP sections exhibited a floor effect, although this is greatly reduced with the NHP-Distress scale. The test-retest reliability was above 0.8 for all sections when patients reporting any change in their health status rating were excluded. Cronbach's alpha coefficients reflected the number of items contained in each section. The internal consistency of the emotional reactions section at one timepoint and the physical mobility section at both timepoints were lower than expected to be higher. All sections except the pain section could be used to distinguish patients who reported their health status to be good or fair from those who rated it to be poor or very poor. CONCLUSION: The adaptation of the NHP for Japanese was successful. Most sections showed reasonable test-retest reliability, indicating that they produced acceptable levels of random measurement error. The internal consistency of the sections was confirmed, although the alpha values of the emotional reactions and physical mobility sections were lower than might be expected for scales of their length. Different sections of the Japanese NHP were shown to have known group validity.
Abstract: We purposed to examine the distribution of the disturbances in the health-related quality of life (HRQoL) and to determine the relationship between HRQoL and various clinical parameters in patients with well-controlled asthma according to the guidelines. We enrolled 162 patients with stable asthma, and 113 were defined as well-controlled. HRQoL was measured by the Living with Asthma Questionnaire (LWAQ), the St. George's Respiratory Questionnaire (SGRQ), and the short-form 36 health survey questionnaire (SF-36), dyspnea by the Medical Research Council (MRC), and psychological status by the Hospital Anxiety and Depression Scale (HADS). In both stable and well-controlled patients, the frequency distributions showed that the scores on the Avoidance, Distress, and Preoccupation constructs on the LWAQ were widely distributed, whereas the scores on the Vitality and General Health scales on the SF-36 were normally distributed. In patients with well-controlled asthma, the HADS had mild to moderate correlations with all questionnaires. Multiple regression analysis showed that the Anxiety, the MRC scale and the treatment steps accounted for 44% of the variance in the Avoidance on the LWAQ. These results suggest that domains of psychological well-being may continue to be affected even though the asthma patients are well-controlled by guideline criteria.
Abstract: STUDY OBJECTIVE: Inhaled bronchodilators are the first-line pharmacotherapy against COPD. The purpose of the present study was to investigate the effects of beta(2)-agonists and anticholinergic agents on the exercise capacity of patients with COPD. METHODS: A total of 67 stable patients with COPD were recruited at the Kyoto University Hospital. After inhaling 400 micro g salbutamol, 80 micro g ipratropium bromide, or an identical placebo in a randomized, double-blind, crossover fashion, the patients performed cycle endurance tests at a constant workload of 80% of the maximum work rate reached on progressive cycle ergometry, and the endurance time was recorded. RESULTS: Both salbutamol and ipratropium bromide significantly improved the endurance time by 29 s (15%; p < 0.001) and 27 s (14%; p < 0.001), respectively, in comparison with the placebo. However, there was no statistically significant difference between them (p = 0.71). The dyspnea ratios were also similarly reduced by both bronchodilators. The difference in the endurance time between therapy with salbutamol and placebo was significantly, but moderately, related to the difference between therapy with ipratropium bromide and placebo. In addition, there were no relationships, or only weakly significant relationships, between the change in FEV(1) and the change in the endurance time, the highest oxygen uptake, and the highest minute ventilation for both salbutamol and ipratropium bromide. CONCLUSIONS: Therapy with both salbutamol and ipratropium bromide improved exercise capacity, as evaluated by the endurance time, and reduced dyspnea similarly in patients with COPD. In addition, the effects of the different bronchodilators on exercise capacity varied within individuals, and a complex mechanism may be responsible for the different effects of these two bronchodilators on exercise capacity vs airflow limitation. These results support the conclusion that both types of inhaled bronchodilators can be used as first-line drugs for the treatment of stable patients with COPD.
Abstract: 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.
Abstract: There is scientific evidence that corticosteroids should be given in exacerbation of COPD. It is still controversial if patients with stable COPD could receive benefits by long-term administration with inhaled corticosteroids. However, many investigators recently consider favorable opinions for inhaled corticosteroids, since inhaled corticosteroids could decrease the frequency of exacerbation especially in severe to moderate COPD.
Abstract: In this study, we analyzed the relationships of exercise capacity and health status to mortality in patients with chronic obstructive pulmonary disease (COPD). We recruited 150 male outpatients with stable COPD with a mean postbronchodilator FEV1 at 47.4% of predicted. Their pulmonary function, progressive cycle ergometry, and health status using the Chronic Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire (SGRQ), and the Breathing Problems Questionnaire were measured at entry. Among 144 patients who were available for the 5-year follow-up, 31 had died. Univariate Cox proportional hazards analysis revealed that the SGRQ total score and the Breathing Problems Questionnaire were significantly correlated with mortality; however, with the Chronic Respiratory Disease Questionnaire, the total score was not significantly correlated. Multivariate Cox proportional hazards analysis revealed that the peak oxygen uptake and the SGRQ total score were both predictive of mortality, independent of FEV1 and age. Stepwise Cox proportional hazards analysis revealed that the peak 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 had different abilities to predict mortality. These results will have a potentially great impact on the multidimensional evaluation of disease severity in COPD.
Abstract: BACKGROUND: Patients with idiopathic pulmonary fibrosis have an increased incidence of lung cancer. The purpose of this study was to determine the outcome of surgical treatment of lung cancer with idiopathic pulmonary fibrosis. METHODS: From January 1992 through December 2001, 64 patients who had simultaneous lung cancer and idiopathic pulmonary fibrosis were treated. Twenty-one (33%) of them underwent surgical resection of lung cancer, and their data were reviewed. RESULTS: There were 56 men and 8 women with an average age of 69 years (range, 43 to 85 years). In the surgical group, there were no early postoperative deaths, and nonfatal complications occurred in 2 patients (10%). Among the 14 patients with stage I cancer, a second primary lung cancer developed in 5 (36%). The causes of death in the surgical group were cancer related in 7 patients, exacerbation of idiopathic pulmonary fibrosis in 7, and other in 2. Five of the 7 patients who died of a cancer-related cause had development of a second primary lung cancer. The actuarial 2-year survival rate of the surgical group was 52% overall, 58% for patients with N0 or N1 disease and 25% for those with N2 disease (p = 0.05). CONCLUSIONS: The long-term results in one surgical group were poor partly because of the high incidence of a second primary lung cancer and partly because of the poor natural history of idiopathic pulmonary fibrosis. These patients require intensive surveillance even after curative resection of lung cancer.
Abstract: 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.
Abstract: One purpose of measuring health status is to predict future outcomes. The aim of this study was to investigate the ability of health status derived from the Chronic Respiratory Disease Questionnaire (CRQ) to predict mortality in chronic obstructive pulmonary disease (COPD). One-hundred and forty-three patients with COPD were recruited. Health status, using the CRQ, and pulmonary function were measured at entry. Mortality after 7 yrs was then assessed. Univariate and multivariate Cox proportional hazards analyses were performed to predict those factors related to mortality. Of all the patients, 13 could not be followed up and 40 had died. The survival rate was 69% at 7 yrs. Univariate regression analyses revealed that the dyspnoea and emotional function domains and the total score of the CRQ were weakly but significantly correlated with mortality from all causes. However, multivariate regression analyses revealed that age and forced expiratory volume in one second were the strongest predictors of mortality, and health status was not a significant factor. Although there was a weak but significant relationship between health status and subsequent mortality in chronic obstructive pulmonary disease, it was not significant after an adjustment for age and pulmonary function. Mortality cannot be predicted from Chronic Respiratory Disease Questionnaire scores.
Abstract: BACKGROUND: Although the health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) has been assessed by generic or disease-specific HRQoL measures, the responsiveness of the generic HRQoL measures is generally weak. OBJECTIVES: To investigate the responses generated by generic and disease-specific HRQoL questionnaires, we prospectively followed the clinical course of patients with newly detected COPD after the initiation of treatment. METHODS: A prospective, longitudinal study with a 1-year follow-up was designed. The forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), the Nottingham Health Profile (NHP) as a generic HRQoL measure, and the Chronic Respiratory Disease Questionnaire (CRQ) as a disease-specific HRQoL measure were measured at baseline and at 3, 6, and 12 months after the initiation of standard treatment. RESULTS: Eighty-two patients completed the study. The FEV(1), FVC, and NHP and CRQ scores improved significantly during the first 3 months (p < 0.05). During the last 6 months, although the FEV(1) declined (p < 0.05), the HRQoL assessed by the NHP and CRQ remained elevated. Except for the score on the social isolation section of the NHP at 12 months, all HRQoL scores at 6 and 12 months were significantly improved compared to baseline (p < 0.05). CONCLUSION: In new patients with COPD, the NHP as well as the CRQ was able to detect changes in the HRQoL associated with effective medical interventions. The influence of the changes in airflow limitation on the HRQoL was weak.
Abstract: BACKGROUND: 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. Study objectives: 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. DESIGN AND METHODS: 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. RESULTS: 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 (p < 0.001). 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). CONCLUSIONS: 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.
Abstract: 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 FEV(1) 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 FEV(1) 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.
Abstract: OBJECTIVE: The purpose of this study was to evaluate the large parenchymal nodules in pulmonary sarcoidosis and to describe a new CT sign termed the "sarcoid galaxy." CONCLUSION: The CT appearance of pulmonary sarcoidosis suggests that the large nodules arise from a coalescence of small nodules. The large nodules are surrounded by many tiny satellite nodules. These findings were considered to simulate the appearance of a galaxy. This observation was supported by radiologic-pathologic correlation. The sarcoid galaxy sign may be a useful adjunct in the diagnosis of pulmonary sarcoidosis.
Abstract: 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.
Abstract: BACKGROUND: There are few long-term studies of the effects of treatment on the natural course of asthma. OBJECTIVE: To investigate the longitudinal changes in airflow limitation and airway hyperresponsiveness (AHR) in asthma. METHODS: We recruited 81 outpatients (never smokers) with stable asthma from the Kyoto University Hospital. They were evaluated for pulmonary function and AHR, expressed by forced expiratory volume in 1 second (FEV1) and the provocation dose that caused a 20% fall in FEV1 (PD20-FEV1), respectively, at entry and every 6 months over 3 years. We used random effects models to estimate the slopes of these changes, and then evaluated the relationship between these changes and their predictive factors. RESULTS: Using random effects models, the percentage of the predicted FEV1 (%FEV1) declined significantly but slightly at a mean rate of 0.5%/year (P = 0.002; 95% confidence interval, 0.3 to 0.8). The mean decline rate of FEV1 was 34 mL/year. However, Log(PD20-FEV1) showed significant improvement at a mean rate of 0.088 cumulative units/year (P < 0.001; 95% confidence interval, 0.053 to 0.122). Multiple regression analysis showed that the baseline values of %FEV1 and Log(PD20-FEV1) were the most significant predictive factors for their subsequent changes, respectively. CONCLUSIONS: In stable asthmatic patients treated according to international guidelines, airflow limitation progressed at a nearly normal rate over 3 years. However, AHR continued to improve despite its ceiling effects. Multiple regression analysis revealed a significant negative relationship between the initial values and the subsequent changes in airflow limitation and AHR, respectively.
Abstract: 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.
Abstract: We analyzed the changes in indices of airway hyperresponsiveness, including hypersensitivity and hyperreactivity, during one year of treatment with inhaled corticosteroids. We then investigated on which of them the inhaled corticosteroids had a primary effect. Fifty outpatients with asthma were recruited and treated with inhaled beclomethasone dipropionate. They underwent bronchoprovocation tests on the initial visit and at 3, 6, and 12 months. The dose of methacholine required to produce a 20% fall in the forced expiratory volume in 1 second (PD20-FEV1) was measured to evaluate airway hypersensitivity. A relatively novel index, the percent change in the forced vital capacity (deltaFVC%) at the PD20-FEV1, was assessed as a marker of airway hyperreactivity. PD20-FEV1 and deltaFVC% were assumed to indicate the horizontal shift of the dose-response curve and the vertical change in the maximal response plateau, respectively. Log(PD20-FEV1) and deltaFVC% continued to improve throughout the year (p < 0.001 and p = 0.002, respectively). Log(PD20-FEV1) improved significantly at the 3-month evaluation (p < 0.001), and deltaFVC% improved at the 6-month evaluation (p = 0.012). Log(PD20-FEV1) had no or weak relationships with deltaFVC% at all evaluation points. In conclusion, inhaled corticosteroids continued not only to reverse the leftward shift of the curve, but also to restore the plateau. Furthermore, their effect was reflected primarily by the former rather than the latter: They should be followed separately to examine how much airway inflammation is reduced.
Abstract: BACKGROUND AND OBJECTIVES: We evaluated the size and configuration of the trachea in patients with chronic obstructive pulmonary disease (COPD; n = 35) on high-resolution computed tomography (HRCT) images and compared them with those of healthy volunteers (n = 24). METHODS: Using a newly developed computed method for analyzing the digital data of HRCT, the size and configuration of the trachea were automatically evaluated. RESULTS: The size of the trachea of the COPD subjects was the same as that of the control subjects; however, the configuration was more distorted in the COPD patients. There was no difference in the tracheal index (TI), which is the ratio of the coronal to the sagittal length, between these two groups; however, the ratio of the short to the long radius (SR/LR) was significantly smaller in the COPD group than in the control group. There was a significant correlation between SR/LR and airflow limitation as assessed by pulmonary function tests in the COPD group. CONCLUSIONS: The SR/LR is a better index of tracheal deformity than the classical TI. This deformity is not a consequence secondary to hyperinflation or emphysematous change of the lung, because the low attenuation area of the lung was not correlated with SR/LR.
Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction caused by emphysema or airway narrowing, or both. Low attenuation areas (LAA) on computed tomography (CT) have been shown to represent macroscopic or microscopic emphysema, or both. However CT has not been used to quantify the airway abnormalities in smokers with or without airflow obstruction. In this study, we used CT to evaluate both emphysema and airway wall thickening in 114 smokers. The CT measurements revealed that a decreased FEV(1) (%predicted) is associated with an increase of airway wall area and an increase of emphysema. Although both airway wall thickening and emphysema (LAA) correlated with measurements of lung function, stepwise multiple regression analysis showed that the combination of airway and emphysema measurements improved the estimate of pulmonary function test abnormalities. We conclude that both CT measurements of airway dimensions and emphysema are useful and complementary in the evaluation of the lung of smokers.
Abstract: The Visual Analogue Scale 8 (VAS8), consisting of eight linear scales, has been developed to measure health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to examine the validity and responsiveness of the VAS8. First, HRQoL was assessed in a cross-sectional study with the VAS8 and the St George's Respiratory Questionnaire (SGRQ) in 46 COPD patients. Relationships between the VAS8 and various physiological parameters were examined. Second, in a longitudinal study, changes in HRQoL scores after pulmonary rehabilitation were evaluated in 29 COPD patients. The total VAS8 scores showed a weak correlation with vital capacity and maximal inspiratory pressure and a moderately strong correlation with 6-min walking distance and dyspnoea rating. The total VAS8 score showed a significant correlation with each SGRQ score. Furthermore, almost every VAS8 and SGRQ score improved significantly after pulmonary rehabilitation. The change in the total VAS8 value showed a strong correlation with that of the SGRQ. The VAS8 is well-suited to assess HRQoL in COPD patients. Visual analogue scales are generally useful in measuring HRQoL in COPD patients, and the VAS8 is particularly beneficial because of its ease of use.
Abstract: Postmortem studies have shown that airway wall thickening is present in asthmatic patients and may play a pathophysiologic role. We investigated the presence and characteristics of airway wall thickening in patients with asthma, using helical computed tomography. Eighty-one asthmatic patients and 28 healthy control subjects were studied cross-sectionally. Airway wall thickness was assessed by a validated method on the basis of wall area (WA), WA corrected by body surface area (WA/BSA), and WA%, defined as (WA/total area) x 100 at the apical bronchus of the right upper lobe. Airway luminal area (Ai) and Ai/BSA were also examined. Asthma duration and severity, pulmonary function, and serum eosinophil cationic protein levels were evaluated. Intraobserver and interobserver reproducibility of WA, WA%, and Ai measurements were good. As compared with control, WA, WA/BSA, and WA% were significantly increased in patients with mild (n = 13), moderate (39), and severe persistent (22) asthma but not in patients with intermittent asthma (7). Comparison of the four asthmatic subgroups demonstrated thicker airways in more severe disease, but no difference in Ai or Ai/BSA. When all asthmatic patients were analyzed together, WA and WA/BSA correlated with the duration, although weakly, and severity of asthma. WA and WA/BSA negatively correlated with FEV(1) (percentage of predicted), FEV(1)/FVC (%), and FEF(25-75%) (percentage of predicted), whereas WA% negatively correlated with only FEV(1). We conclude that airway wall thickening occurs in patients with asthma and is not limited to those with severe disease. The degree of airway wall thickening may relate to the duration and severity of disease and the degree of airflow obstruction.
Abstract: BACKGROUND: We hypothesized that the factors which may influence health status would differ in patients at different disease stages of chronic obstructive pulmonary disease (COPD). The present study investigated how impairments in health status were distributed in male patients at each disease stage according to the British Thoracic Society (BTS) guidelines, and analysed the contribution of the clinical indices, the dyspnoea rating and the psychological status to the health status of patients at the three disease stages of COPD. METHODS: A total of 218 consecutive male patients with stable COPD were recruited from our outpatient clinic. All eligible patients completed pulmonary function testing, progressive cycle ergometry, a dyspnoea rating [Medical Research Council (MRC) dyspnoea scale], an assessment of their anxiety and depression [Hospital Anxiety and Depression Scale (HADS)], and an assessment of their health status [the St. George's Respiratory Questionnaire (SGRQ)]. The patients were categorized into three groups: mild COPD with a FEV1 at 60-79% of the predicted value, moderate COPD at 40-59% of the predicted value, and severe COPD at below 40% of the predicted value. RESULTS: Twenty-five patients (11%) had mild COPD, 72 patients (33%) had moderate COPD, and 121 patients (56%) had severe COPD. Significant differences were observed for the total score and for three components on the SGRQ among patients at the three stages (one-way ANOVA, P<0.05). The scores for the total SGRQ and for the activity component were significantly higher for patients with severe COPD than for patients with moderate COPD [Fisher's least-significant-difference (LSD) method, P<0.05], and also significantly higher for moderate COPD patients than for mild COPD patients. The maximal oxygen uptake (VO2 max) correlated significantly with the total SGRQ score in the mild patients [Pearson's correlation coefficient (r) = -0.67], but not in the moderate or severe patients. The MRC dyspnoea scale had strong correlations with the SGRQ in all patient groups (r = 0.53 to approximately 0.70). Anxiety and depression on the HADS showed moderate correlations with the SGRQ score in the mild and severe patients (r = 0.51 to approximately 0.57). Multiple regression analysis showed that in patients with mild COPD, the MRC and VO2 max accounted for the total score on the SGRQ. Anxiety on the HADS plus the MRC scale accounted for the total score on the SGRQ in patients with moderate COPD, and anxiety on the HADS, the MRC scale and the FEV1 significantly influenced the SGRQ severe COPD patients. CONCLUSIONS: The disease staging proposed by the BTS guidelines can separate patients with COPD according to impairments in their health status. Furthermore, the factors that influence health status differed in patients at the three disease stages. Our findings support the boundaries used in disease staging and some recommendations from the BTS guidelines.
Abstract: 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) = 40.8 +/- 16.5% predicted; mean +/- 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 microg 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 (V 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.
Abstract: Chronic obstructive pulmonary disease (COPD) is a basically benign disease, but the prognosis is so poor that the mortality rate is similar to some malignant diseases. Depending on the disease severity, the 5-year mortality rate of patients with COPD varies from 40 to 70%. The three major causes of death have been identified as COPD itself, lung cancer, and cardiovascular disease. The following factors have been reported to be related to survival: FEV1 (especially the maximal attainable lung function), age, gender, PaO2, PaCO2, body weight, and comorbidity. There have been several large-scale randomized clinical trials to examine the prophylactic effects of inhaled anti-cholinergics and inhaled corticosteroids on the annual decline in FEV1. However, unfortunately, in all of the published studies, these drugs had no effect on the annual decline in FEV1.
Abstract: It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.
Abstract: BACKGROUND: In spite of the known role of cigarette smoking in the development of airflow limitation (AL), fewer than 20% of smokers actually develop chronic obstructive pulmonary disease (COPD). OBJECTIVES: We examined how smoking histories and indices in blood are related to the degree of AL in asymptomatic smokers in order to determine whether they can predict the development of AL. METHODS: Spirometry and peripheral blood tests were examined in 433 Japanese asymptomatic current smokers at the initial examination. Forced expiratory volume in 1 s (FEV(1)) was measured periodically for 2 or more years (2-13 years) in 66 of the subjects. RESULTS: AL defined as an FEV(1)/vital capacity of less than 0.7, was found in 11.3% (49 of 433) of the smokers. Pack-years of smoking, serum amounts of alpha(1)-proteinase inhibitor, and serum procollagen III peptide activities were correlated with the degree of AL. Fifteen percent (10 of 66) of subjects underwent rapid declines in FEV(1) that were found to be related not with smoking amounts or initial FEV(1), but with low FEV(1) (%pred) adjusted by pack-years and an elevated serum neutrophil elastase/alpha(1)-proteinase inhibitor ratio. These results suggest that smokers with a low FEV(1) out of proportion to pack-years are susceptible smokers at a high risk of developing COPD, and further, that increased proteinase burden relative to antiproteinase activity may contribute to the development of COPD. CONCLUSIONS: We conclude that the serum neutrophil elastase/alpha(1)-proteinase inhibitor ratio and FEV(1) (%pred) adjusted by pack-years can be reliable predictors of the development of COPD.
Abstract: The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.
Abstract: A novel, short, and simple questionnaire, the Airways Questionnaire 20 (AQ20), has been developed to measure and quantify disturbances in the health-related quality of life (HRQoL) of patients with asthma or chronic obstructive pulmonary disease (COPD). The AQ20 has 20 items with yes/no responses, and should take 2 min to complete and score. The purpose of this study was to assess the discriminative properties and responsiveness of the AQ20 in patients with COPD. First, in a cross- sectional study, 165 patients with mild-to-severe COPD (mean age, 69 +/- 7 yr; FEV1, 40 +/- 16% of predicted) completed the AQ20, the St. George's Respiratory Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ), pulmonary function tests, a progressive cycle ergometer exercise test, and an assessment of their dyspnea and anxiety. The score distribution of the AQ20 was skewed toward the mild end of the scale, whereas the SGRQ and CRQ showed a normal distribution. The AQ20 showed a moderately strong correlation with the maximal oxygen uptake and the assessment of dyspnea (Spearman's correlation coefficients [rs] = -0.49, -0.60, respectively), but a weak correlation with the FEV1 (rs = -0.18). Moderate to strong correlations were also recognized between the AQ20 and SGRQ and CRQ (rs = -0.80, -0.72, respectively). Multiple regression analysis revealed that dyspnea and anxiety accounted for 43% of the variance in the AQ20, almost the same as in the SGRQ and CRQ. Second, longitudinal changes over time in the FEV1, AQ20, SGRQ, and CRQ were examined in 86 patients with newly detected COPD (mean age, 69 +/- 8 yr; FEV1, 45 +/- 19% of predicted). All three measures showed significant improvements in their scores over a 3-mo period after initiating medical intervention. The change in the AQ20 showed a moderate to strong correlation with each dimension of the SGRQ and CRQ (rs = 0.56, -0.52, respectively), but no significant correlation was noted with the FEV1. In conclusion, the AQ20 may have discriminative properties and responsiveness that are similar to more complex questionnaires such as the SGRQ and CRQ. Because it is short and can be quickly answered and scored, the AQ20 may be useful in studies with limited time for HRQoL assessments.
Abstract: STUDY OBJECTIVES: To compare categorizations of the level of dyspnea with the staging of disease severity as defined by the FEV(1) 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 alpha-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 (FEV(1), 35 to 49% predicted) and stage III disease (FEV(1), < 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.
Abstract: BACKGROUND: The benefits of inhaled corticosteroids in the management of COPD are less apparent than they are in asthma therapy, and the potential for adverse systemic effects of high-dose inhaled corticosteroids has been recognized recently. It is therefore essential to know the maximal obtainable benefits in order to assess the risk/benefit ratio of this treatment. PURPOSE: The aim of this study was to investigate the maximal obtainable benefits of high-dose inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used in combination with adequate doses of regular bronchodilators in patients with stable COPD. STUDY DESIGN: Thirty patients with stable COPD completed a randomized, double-blind, placebo-controlled cross-over trial with either 3 mg/d of BDP or with a matching placebo using a metered-dose inhaler with a spacer device for 4 weeks during each treatment period. All of the patients continued to inhale both 400 microg of salbutamol qid and 80 microg of ipratropium bromide qid. RESULTS: The mean prebronchodilator FEV1 was 0.97+/-0.35 L during the placebo period and 1.08+/-0.38 L during the BDP period (p < 0.001). While on BDP, five patients demonstrated a response in their FEV1 of more than 8.5% of the predicted value, which was above the range that covered 95% of the distribution of the placebo response. The mean absolute improvement in the FEV1 in these 5 objective responders was 0.34+/-0.10 L, compared to 0.06+/-0.09 L in the 25 objective nonresponders. Symptom scores for wheezing and dyspnea were significantly better with BDP than with placebo. Hoarseness and sore throat were associated more with BDP treatment. CONCLUSION: Although a considerable minority of patients benefited substantially from this treatment, the overall outcome does not seem to justify the widespread use of this treatment in the light of increasing recognition of the potential adverse systemic effects of high-dose inhaled corticosteroids.
Abstract: BACKGROUND: The low attenuation areas on computed tomographic (CT) scans have been reported to represent emphysematous changes of the lung. However, the regional distribution of emphysema between the inner and outer segments of the lung has not been adequately studied. In this study the regional distribution of low attenuation areas has been compared by quantitative CT analysis and the contribution of the regional distribution to pulmonary function tests evaluated in patients with chronic obstructive pulmonary disease (COPD). METHODS: Chest CT images and the results of pulmonary function tests were obtained from 73 patients with COPD. The lung images were divided into inner and outer segments in the upper (cranial), middle, and lower (caudal) sections. The percentage ratio of low attenuation area to corresponding lung area (LAA%) was then calculated. The LAA% of each segment was also compared with the results of pulmonary function tests. RESULTS: The mean (SD) LAA% of the inner segment was 39.1 (18.5) compared with 28.1 (13.2) for the outer segment (p<0.0001). Linear and multiple regression analyses revealed that airflow limitation is closely correlated with the inner segment LAA% of the lower lung. In contrast, the carbon monoxide transfer factor is closely correlated with the inner segment LAA% of the upper lung. CONCLUSION: Low attenuation areas on CT scans are more often found in the inner segment of the lung than in the outer segment, and the contribution of the inner segment to pulmonary function tests may be greater than the outer segment.
Abstract: Increases in the low attenuation areas (LAA) of chest x-ray computed tomography images in patients with chronic obstructive pulmonary disease (COPD) have been reported to reflect the development of pathological emphysema. We examined the statistical properties of LAA clusters in COPD patients and in healthy subjects. In COPD patients, the percentage of the lung field occupied by LAAs (LAA%) ranged from 2.6 to 67.6. In contrast, LAA% was always <30% in healthy subjects. The cumulative size distribution of the LAA clusters followed a power law characterized by an exponent D. We show that D is a measure of the complexity of the terminal airspace geometry. The COPD patients with normal LAA% had significantly smaller D values than the healthy subjects, and the D values did not correlate with pulmonary function tests except for the diffusing capacity of the lung. We interpret these results by using a large elastic spring network model and find that the neighboring smaller LAA clusters tend to coalesce and form larger clusters as the weak elastic fibers separating them break under tension. This process leaves LAA% unchanged whereas it decreases the number of small clusters and increases the number of large clusters, which results in a reduction in D similar to that observed in early emphysema patients. These findings suggest that D is a sensitive and powerful parameter for the detection of the terminal airspace enlargement that occurs in early emphysema.
Abstract: PURPOSE: To address the optimal scanning condition of high resolution computerized tomography from the perspective of minimizing exposed dose. METHOD: The influence of the electric current, the slice number, and the slice thickness on precise percent ratio of the low attenuation area to whole lung field (LAA%) of chronic obstructive pulmonary disease patients was examined. The standard conditions were 250 mA, 3 slices, 2 mm slice thickness, and a varied parameter. RESULTS: In cases showing an LAA% less than 30, LAA% obtained by < or =150 mA were significantly larger than those by 250 mA. The mean LAA% with 3 and 10 slices were well correlated and the correlation with lung function was similar. The correlation of LAA% with lung function was approximately the same between the 2 and 5 mm slice thicknesses. CONCLUSION: The electrical current must be > or =200 mA, and 3 slices and 2 mm slice thickness are appropriate.
Abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity in Western countries, and is the fourth leading cause of death in North America. A number of the guidelines regarding the management and treatment of COPD have been published in recent years. These guidelines were generated in response to the fact that COPD is a major cause of mortality and morbidity, and remains an important social problem. In the guidelines, COPD is defined as a disorder characterized by airflow limitation due to chronic bronchitis and emphysema; the airflow limitation progresses slowly, and does not change markedly over several months.
Abstract: Three disease-specific, health-related quality of life (HRQL) questionnaires have been introduced to assess patients with chronic obstructive pulmonary disease (COPD): the St. George's Respiratory Questionnaire (SGRQ), the Breathing Problems Questionnaire (BPQ), and the Chronic Respiratory Disease Questionnaire (CRQ). The purpose of the present study was to make comparisons between the SGRQ, the BPQ, and the CRQ in their discriminative properties, and to clarify the characteristics of each questionnaire. One hundred forty-three patients with mild to severe COPD completed pulmonary function tests, progressive cycle ergometer testing for exercise capacity, assessment of dyspnea, anxiety, and depression, and assessment of HRQL. The frequency distributions of the questionnaire scores showed that the SGRQ and the CRQ were normally distributed and that the BPQ was skewed toward low scores. Relationships between all dimensions of the three questionnaires were significant (correlation coefficients [Rs] = 0.74 to 0.86). The three questionnaires had significant but weak correlations (Rs = -0.24 to -0.36) with some physiologic variables (VC, FEV1, and DL(CO)/VA) and mild to moderate correlations with exercise capacity and assessment of dyspnea, anxiety, and depression. Stepwise multiple regression analyses revealed that the Baseline Dyspnea Index (BDI) score, anxiety by the Hospital Anxiety Depression Scale (HAD), and maximal oxygen uptake (VO2max) accounted for 61% of the variance in the SGRQ and that the BDI and anxiety of the HAD accounted for 53 and 49% of the variance in the BPQ and the CRQ, respectively. Dyspnea and psychologic status impacted the HRQL in patients with COPD. Although no substantial differences between the SGRQ, the BPQ, and the CRQ were evident in the correlations with physiologic parameters and the influential factors, the BPQ was found to be less discriminatory than the SGRQ and the CRQ in evaluating HRQL cross-sectionally.
Abstract: Exacerbations of chronic obstructive pulmonary disease (COPD) are usually treated with bronchodilator therapy, glucocorticoids and antibiotics. However, there are few experimental data on the effects of these agents in patients with acute COPD. A beta(2)-adrenoceptor agonist is usually given first because it can be expected to produce a rapid response. An anticholinergic agent should also be given when the patient is severely ill or responds inadequately to the beta(2) agonist. These agents can be administered via a nebuliser or using a metered-dose inhaler in conjunction with a spacer device. Glucocorticoids can accelerate recovery if the standard empirical regimens for acute exacerbations of asthma are used, although a longer treatment duration appears to be required. Theophylline provides little additional benefit in patients who receive frequent doses of inhaled bronchodilators and an adequate dosage of a glucocorticoid. Although the role of bacterial infections is not completely understood, the use of antibiotics is justified in patients with severe airflow limitation who have febrile tracheobronchitis.
Abstract: Ambulatory peak flow monitoring plays an important role in the diagnosis and management of patients with bronchial asthma. Today several kinds of portable peak flow meters (PFMs) are available for this purpose and sometimes comparisons between the readings of different kinds of PFMs are necessary in clinical setting. We compared four types of PFMs in patients with various respiratory diseases. The study population consisted of 294 patients with asthma, chronic obstructive pulmonary disease, diffuse panbronchiolitis and other respiratory systems, and 15 healthy volunteers. Initially, subjects underwent a spirometry until at least three acceptable forced expiratory curves were obtained. Thereafter each subject blew into a Mini-Wright meter, Assess meter, Pulmo-graph meter and Wright Pocket meter, three times in a random order, with an interval of 4 min. The highest value of three blows was recorded in each PFM measurement. Finally, a second set of spirometric measurements were obtained. Spirometric peak flow rates (PEFRs) were obtained from the best single test which gave the largest sum of forced vital capacity and forced expiratory volume in 1 s (FEV1). In cases when FEV1 in the first spirometry examination was less than 11 or the readings of the PFM were less than 3501 min-1, low-range PFMs were used. The second spirometric PEFR was used as a standard against which the reading of the PFM was compared. The correlation coefficients between the readings of each PFM and spirometric PEFR did not differ significantly from each other. The limits of agreement between each PFM were very wide. In both low- and standard-range PFM, the Assess meter had a significantly greater absolute difference from the spirometric PEFR than other PFMs. In the standard range, the Wright Pocket meter also had a greater difference than the Pulmo-graph meter. The standard-range Assess meter tended to lose its strength of correlation with the spirometric measurement at higher flow rates as did the low-range Pulmo-graph and Mini-Wright meters at the lower and higher flow rates, respectively. All four types of standard-range PFMs gave similarly valid values when spirometric PEFR was used as a reference. However, the limit of agreement between each PFM is so wide that we do not recommend the use of the readings of each meter interchangeably.
Abstract: Health-related quality of life is usually impaired in patients with moderate to severe chronic obstructive pulmonary disease. The Sickness Impact Profile, the Medical Outcome Study "short form" 36, and the Nottingham Health Profile have all been used as generic measures of health-related quality of life. Although the discriminative properties of three disease-specific instruments, the Chronic Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire, and the Breathing Problems Questionnaire, are similar, the responsiveness of the Chronic Respiratory Disease Questionnaire and the St. George's Respiratory Questionnaire has been the most clearly demonstrated. The characteristics of each instrument should be considered in the selection of specific health-related quality of life questionnaires for clinical research.
Abstract: The aim of the study was to assess the effect of treatment on health-related quality of life (HRQoL) in patients with asthma. We used the Japanese version of the Living With Asthma Questionnaire (LWAQ) as an asthma-specific HRQoL measure. Thirty-four new patients were enrolled and treated according to Guidelines on the Management of Asthma by the British Thoracic Society. The LWAQ and spirometry were evaluated on the initial visit, and three and six months after treatment. The LWAQ score, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were significantly improved three months after treatment. The Japanese version of the LWAQ was reliable. For the first three months, there were no correlations between changes in FEV1 or FVC and LWAQ scores (Rs = 0.11-0.25). Pulmonary functions could not predict HRQoL well. Therefore, HRQoL should be measured directly to assess HRQoL in asthmatics.
Abstract: Computed tomography (CT) is used to detect emphysematous changes in the lungs of living patients. It is therefore important to develop a standard method for the radiographic quantification of emphysematous lesions using CT. The authors determine the best CT scanning methods for assessing the degree of pulmonary emphysema. Computed tomography scanning was performed in 85 consecutive patients with stable chronic obstructive pulmonary disease. Scans were obtained using 2-mm or 5-mm collimation, at full inspiration or full expiration, and with standard or high spatial-resolution reconstruction images (eight images each). Emphysema was then assessed by visual scoring using a five-point scale for each lung. Emphysema was scored as significantly less severe using standard reconstruction images. There were no significant differences in CT-scored emphysema on scans obtained with 2-mm and 5-mm collimation. Emphysema was scored as significantly less severe on expiratory scans. The postbronchodilator forced expiratory volume in one second value correlated better with emphysema scored on expiratory scans. Computed tomography-scored emphysema obtained by all methods correlated well with the diffusion capacity and total lung capacity, regardless of the method used. Using a visual scoring system with a five-point scale, narrow collimation is probably not necessary for the quantification of emphysema, although a high spatial-resolution reconstruction appears to be of value. Scans obtained in exhalation appear to underemphasize the severity of emphysema.
Abstract: This investigation studied the general conditions and prognostic factors of pulmonary epithelioid haemangioendothelioma (PEH), which is a rare disease. Twenty-one patients were collected throughout Asia by a questionnaire. Age at the detection or onset of symptoms of PEH was 14-64 yrs (mean 44 yrs). Males were more likely to be detected by symptoms (4/8, 50%) than were females (1/13, 8%). Fifteen showed bilateral multiple nodular opacities. Partial spontaneous regression occurred in three asymptomatic patients (one male and two females, all with bilateral multiple nodular opacities) 5, 13 and 15 yrs after detection. Two of the three patients with pleural effusion died within 1 yr, while the 16 patients with no effusion were alive more than 1 yr later (p<0.05). Histologically, two patients with fibrinofibrous pleuritis and extrapleural proliferation of tumour cells died within 2 yrs, while only one of 14 patients lacking such manifestations died within the same period (p<0.05). All three patients without spindle tumour cells survived for 12 yrs after the diagnosis, while all four patients with such cells died during the same period (p<0.05). In conclusion, 21 patients with pulmonary epithelioid haemangioendothelioma were reported, of whom three demonstrated partial spontaneous regression, and adverse prognostic features were identified.
Abstract: BACKGROUND: The effects of theophylline or anticholinergic agents on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) remain controversial. The aim of the present study was to compare the effect of an oral theophylline with an inhaled anticholinergic agent and to examine the effects of combined therapy on exercise performance using progressive cycle ergometry. METHODS: Twenty one men with stable COPD and a mean (SD) forced expiratory volume in one second (FEV1) of 1.00 (0.40) 1 were studied. Theophylline (600 or 800 mg daily), ipratropium bromide (160 micrograms), a combination of both drugs, and placebo were given in a randomised, double blind, four period crossover design study. Spirometric data, pulse rate, and blood pressure were assessed before and at 90 and 120 minutes after inhalation. Symptom limited progressive cycle ergometer exercise tests (20 watts/min) were performed 90 minutes after each inhalation, and dyspnoea was measured during exercise using the Borg scale. RESULTS: The mean (SD) serum theophylline concentration was 18.3 (6.3) micrograms/ml, and seven patients had side effects during treatment with theophylline. Theophylline and ipratropium bromide produced greater increases in FEV1, maximal oxygen consumption, maximal minute ventilation, and several dyspnoea ratios than placebo. There were no differences between theophylline and ipratropium bromide except in maximal heart rate. A combination of both drugs produced greater improvements in pulmonary function and exercise capacity than either drug alone. CONCLUSIONS: Both high dose theophylline and high dose ipratropium bromide improved exercise capacity in patients with stable COPD. Although data based on short term effects cannot be directly applied to long term therapy, theophylline added to an inhaled anticholinergic agent may have beneficial effects on exercise capacity in patients with COPD.
Abstract: A 21 yr old with deep breathing and awake apnoea, who had recurrent hypoxaemia and hypercapnia without sleep apnoea, was presented. Although the organic abnormality responsible for the breathing disturbance was not found, administration of acetazolamide facilitated several breaths between sighs, and the patient's hypoxaemia with hypercapnia improved. Some patients who have abnormalities in the cortical control of breathing that cannot be detected by present methods of examination may experience some improvement in breathing with the administration of chemical stimulants such as acetazolamide.
Abstract: Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.
Abstract: BACKGROUND AND AIM OF THE WORK: Hypersensitivity pneumonitis (HP) is a granulomatous lung disease characterized by a T lymphocyte bronchiolalveolitis and in several recent studies the preferential use of V beta regions of T-cell receptor (TCR) has been demonstrated. In Japan, summer-type HP, caused by Trichosporon cutaneum, is the most prevalent type of HP, and it is known by the familial occurrence. To clarify whether TCR expression could be restricted on lung T-cell and associate with the HLA type in an organic antigen-driven hyperimmune status, we examined three cases of summer-type HP in one Japanese family. METHODS: TCR expression on bronchoalveolar lavage (BAL) fluid T-cells was analyzed with 13 TCR V gene specific monoclonal antibodies. In addition, HLA types were analyzed using the microlymphocyte toxicity method. RESULTS: The changes in TCR expression were most frequently found in the BAL fluid CD8+ subset, but we found no preferential TCR V gene usage common to the three cases or correlation between the HLA type and the V gene usage. In two of the three cases who underwent a second lavage three months after the first one, some of the TCR expansions were preserved. CONCLUSION: Preferential usage of several TCR V genes was observed in three cases with summer-type HP in one family, but we could find neither a common T cell expansion nor any correlation between the HLA type and the TCR V gene usage.
Abstract: The American Thoracic Society (ATS) and the European Respiratory Society (ERS) recommend that the largest forced vital capacity (FVC) and the largest forced expiratory volume in 1 s (FEV1) should be recorded from at least three acceptable curves independently which curve they came from. Although these recommendations have been used for decades, there is still some controversy over their validity. The purpose of this study was to determine how the intersession variability of reported FVC and FEV1 values is influenced by different methods of selection in clinical practice. The study population consisted of 283 patients with obstructive airway diseases. Spirometry was performed until three acceptable forced expiratory curves were obtained in the standing position. A second set of spirometric measurements was obtained approximately 30 min after the first set of measurements. The following sampling methods were compared: method A, the largest FVC and the largest FEV1 among all three acceptable curves (ATS-ERS recommendation); method B, the FVC and the FEV1 from the single curve that yielded the largest sum of FVC plus FEV1 (best test); method C, the average of all three acceptable curves; method D, the average of the largest two FVCs and FEV1s among all of the three acceptable curves. FVC and FEV1 determined by method B gave almost identical values to those obtained by method A in most cases. However, method A was least variable for FEV1. In addition, the differences in FEV1 values between these two methods were large in some of patients with chronic obstructive pulmonary disease. The other selection criteria compared in this study offer no clear-cut advantages over method A. The ATS ERS recommended method appeared to be slightly more reproducible than the other selection criteria, including the 'best test' method, and should therefore be the preferred method of choice.
Abstract: When dyspnea must be assessed clinically, there are three methods of assessment: the measurement of dyspnea with activities of daily living using clinical dyspnea ratings such as the modified Medical Research Council (MRC), the Baseline Dyspnea Index (BDI), and the Oxygen Cost Diagram (OCD); the measurement of dyspnea during exercise using the Borg scale; to assess the influence of dyspnea on health-related quality of life (HRQoL) using disease-specific questionnaires such as the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ). The purpose of the present cross-sectional study was to clarify relationships between dyspnea ratings and HRQoL questionnaires by applying factor analysis. One hundred sixty-one patients with mild to severe COPD completed pulmonary function tests, progressive cycle ergometer testing for exercise capacity, assessment of dyspnea, HRQoL, anxiety, and depression. Factor analysis demonstrated that the MRC, BDI, OCD, and Activity of the SGRQ, and Dyspnea of the CRQ, were grouped into the same factor, and the frequency distribution histograms of these five measures showed virtually the same distribution. The Borg scale at the end of maximum exercise was found to be a different factor. The MRC, BDI, OCD, and Activity in the SGRQ, and Dyspnea in the CRQ demonstrated the same pattern of correlation with physiologic data, and they had significant relationships with FEV1 (correlation coefficients [Rs] = 0.31 to 0. 48) and maximal oxygen uptake (Rs = 0.46 to 0.60). Disease-specific HRQoL questionnaires, the SGRQ and the CRQ, which contain a specific dimension for evaluating dyspnea, may be substituted for clinical dyspnea ratings in a cross-sectional assessment. Dyspnea rating at the end of exercise may provide further information regarding dyspnea.
Abstract: An automated and quantitative assessment of the spatial distribution of low attenuation areas (LAA) on X-ray CT was performed using texture analysis in chronic pulmonary emphysema (CPE) patients. LAA was defined as those areas having a density less than the mean minus one SD of the control (-960 HU). The probability of change from non-LAA to LAA between a given pair of pixels with horizontal intervals of i pixels (RNi) was evaluated, because this reflects the interaction between LAA and non-LAA regions with different resolutions. The relationship between the percentage area of the LAA over the total area of the entire lung field (LAA%) was subsequently estimated. The RNi increased sharply as the i value increased from 1 to 5, but then almost became a plateau for i values larger than 5. This suggests that the fundamental structures in the LAA areas ranged from 1 x 1 to 5 x 5 pixels in size. RN1-LAA% and RN5-LAA% plots produced curves which were convex, with peak values at approximately 50 LAA% of 0.09 and 0.18, respectively. In the RN5/RN1-LAA% plot, the RN5/RN1 ratio remained constant at 2.0 regardless of the LAA%. A random process simulation was performed to determine the patterns of LAA proliferation if the spatial distribution of the LAA units was random. When the unit size was kept constant, the results of the simulation did not fit the empirical relationship between the LAA% and the three parameters (RN1, RN5 and RN5/RN1). The simulation provided the best-fitting curves when the unit size of the LAA increased in proportion with the LAA%, starting from a 1 x 1 pixel size increasing at a ratio 1 x 1/(5 LAA%). This suggested that the LAA units do not proliferate randomly in spatial orientation at a fixed unit size, but rather spread throughout the whole lung field in a congregated form whilst increasing their unit size. Thus, it may be concluded that healthy lung tissues near emphysematous lesions have a high probability of suffering from emphysema in the future. This may be due to a direct effect of the neighboring emphysematous lesion or due to a pathologic change in the larger bronchii which dominate both the healthy tissues and the emphysematous lesions.
Abstract: Effects of reducing or stopping inhaled beclomethasone dipropionate (BDP) on airway hyperresponsiveness (AHR) were evaluated in stable chronic asthma. In 16 patients, after the best control (no symptoms, peak expiratory flow rate [PEF] > 80% best) was achieved for at least 3 months, the dose of BDP was reduced to 2/3 to 1/2. No differences were observed in the mean FEV1, PEF and AHR between before and 3 months after the reduction of BDP. In 7 patients, after the almost normal level of AHR was achieved, the dose of BDP was gradually reduced and then discontinued. Three out of the 7 patients had maintained the adequate level of AHR over 14 months, but in the other 4 patients AHR deteriorated below normal level and re-administration of BDP was needed due to worsening of symptoms and PEF. In conclusion, a gradual reduction of the dose of BDP is possible, if the best control is achieved for at least 3 months. The possibility of discontinuation of BDP may exist in some patients after achieving adequate AHR.
Abstract: BACKGROUND: Although the bronchodilating effect of inhaled anticholinergics has been established in patients with chronic obstructive pulmonary disease (COPD), their effects on exercise capacity are still controversial. Previous studies have suggested that the standard dosage hardly affects exercise tolerance, whereas higher doses might elicit an improvement. The aim of the present study was to determine the dose of ipratropium bromide aerosol that improves exercise performance using progressive cycle ergometry in patients with stable COPD. METHODS: Twenty men with stable COPD of mean (SD) age 69.2 (4.6) years and forced expiratory volume in one second (FEV1) 1.00 (0.37) 1 were studied in a randomised double blind manner. Each patient received ipratropium bromide in doses of 240 micrograms, 160 micrograms, 80 micrograms, 40 micrograms, and placebo from a metered dose inhaler (MDI) with an InspirEase spacer on five separate days. Spirometric parameters were assessed before and at 30, 60, 90, and 120 minutes after each inhalation, and pulse rate and blood pressure were also measured immediately before each spirometric measurement. Symptom limited progressive (20 watts/min) cycle ergometer exercise tests were performed 90 minutes after each inhalation. RESULTS: Ipratropium bromide in doses of 160 micrograms and 240 micrograms produced a greater increase in FEV1 than 40 micrograms or 80 micrograms ipratropium bromide at all time points. Doses of 160 micrograms and 240 micrograms ipratropium bromide also produced greater increases in maximal work load and maximal oxygen consumption than placebo, whereas 40 micrograms and 80 micrograms ipratropium bromide did not. There was a weak correlation between the change in FEV1 and the change in maximal work load (r = 0.45). No differences were found in pulse rate or blood pressure between the treatment and placebo groups, and no side effects were noted throughout the study. CONCLUSIONS: A dose of at least four times the standard dose of ipratropium bromide from an MDI with a spacer device was necessary to improve maximal cycle exercise capacity in patients with stable COPD. Although the data from cycle ergometry cannot be directly applied to exercise performed during day to day activities, it is conceivable that the recommended doses of ipratropium bromide do not elicit the optimal clinical benefits.
Abstract: In a cross-sectional study, we evaluated success in the control of asthma as defined by criteria for symptoms, for FEV1/FVC, and for peak flow rates. One hundred and three patients with chronic asthma who had been treated with inhaled steroids were studied. Chest tightness, dyspnea, wheezing, sputum production, and coughing were each scored from 1 (worst) to 5 (best). Symptoms were said to have been controlled if the symptoms scores for the preceding 4 weeks were greater than or equal to 20; FEV1/FVC was said to be under control if it was greater than or equal to 70% when measured in the clinic; peak flow was said to have been controlled if the lowest peak flow in the preceding 4 weeks was greater than or equal to 80% of the highest measured value. Symptoms were controlled in 72% of the patients, FEV/FVC was under control in 83%, and peak flow was controlled in 66%. The patients were grouped by severity of disease into four classes, and these percentages did not differ significantly among the classes. In 22 out of 74 (30%) patients in whom symptoms were controlled, peak flow was not controlled. Furthermore, in 18 out of 64 (28%) patients in whom symptoms and FEV/FVC were controlled, peak flow was not controlled. We concluded that in treating asthma, not should symptoms be controlled, but peak flow should also be measured each day to avoid undertreatment.
Abstract: STUDY OBJECTIVE: Bronchial hyper-responsiveness (BHR) is widely observed in patients with chronic obstructive pulmonary disease (COPD). However, its clinical significance in COPD has not yet been established. To determine the factors that influence BHR in COPD, multiple linear regression analysis was used to analyse the relationship between BHR to methacholine and baseline forced expiratory volume in 1 s (FEV1), vital capacity (VC), residual volume (RV)/total lung capacity (TLC), static compliance (Cst), transfer coefficient of the lung (Kco), and the percentage of low attenuation area (%LAA) determined by computed tomographic (CT) scan. METHODS: Bronchial responsiveness to methacholine was determined in 63 patients with COPD by the dosimeter method and expressed as PD20FEV1. Residual volume and TLC were determined by body plethysmography. The percentage of low attenuation area was defined as the percentage of area less than -960 Hounsfield unit on a CT scan of the thorax. RESULTS: Forced expiratory volume in 1s (%predicted) and %LAA correlated with BHR (P = 0.023 and 0.020, respectively), while VC (%pred), RV/TLC, Cst and Kco did not. The coefficient of determination was 0.43. The regression analysis showed that a 10% increase in FEV1 (%pred) and a 10% decrease in %LAA would increase log(PD20FEV1) by 0.145 and 0.117, respectively. CONCLUSIONS: A considerable proportion of the BHR in COPD is related to functional abnormalities and morphologic changes of emphysema, such as decreased baseline airway calibre and destruction of the lung parenchyma.
Abstract: In asthmaticus with relatively stable control, inhaled beta agonists are the primary drugs used to relieve symptoms which are mild and does not necessitate patients to visit emergency rooms. Global strategy for asthma management and prevention NHLBI/WHO workshop report gives inhaled beta agonists a specific position as a "reliever". Long-acting beta agonists such as salmeterol and formoterol were developed as a compensatory drug for "controllers". They have prolonged duration of bronchodilation effects with more than 12 hours. When asthmatic patients given high doses of inhaled corticosteroids do not enjoy best management, oral slow-releasing theophylline would be considered as one of next additional drugs of choice.
Abstract: STUDY OBJECTIVE: To determine the physiologic factors that influence the health-related quality of life (HRQL) in patients with stable COPD and to identify the factors that most influence HRQL. METHODS: The Nottingham Health Profile (NHP) was used as a general HRQL measure and the Chronic Respiratory Disease Questionnaire (CRQ) was used as a disease-specific HRQL measure to investigate 132 patients with stable COPD, and measurements of HRQL were compared with physiologic measures. RESULTS: Vital capacity, FEV1, the ratio of the FEV1 to the FVC, diffusion capacity for carbon monoxide, diffusion capacity corrected for alveolar volume, lifetime cigarette consumption expressed as pack-years, and age were weakly correlated with several dimensions of both the NHP and the CRQ. Factor analysis reduced these variables to three factors. Two factors mainly referring to airflow limitation and diffusing capacity were weakly correlated with several dimensions of both the NHP and the CRQ. Logistic regression analysis identified 4 independent predictors of HRQL: airflow limitation (odds ratio [OR] = 0.59 to 0.69), diffusing capacity (OR = 0.75 to 0.82), pack-years (OR = 1.20 to 1.23), and age (OR = 2.13). The CRQ was more sensitive to impairment of HRQL than the NHP. CONCLUSIONS: The HRQL of patients with stable COPD is partly determined by airflow limitation, diffusing capacity, pack-years, and age. However, these factors could not predict the whole spectrum of HRQL, and the contribution of these factors to HRQL was limited. Therefore, HRQL should be measured directly in addition to physiologic measures.
Abstract: One dose of an anticholinergic agents has about the same bronchodilatory effect as one of a beta 2-agonist. Anticholinergic agents may be used first in patients with stable chronic obstructive pulmonary disease, because of the possible adverse effects of beta 2-agonists. One puff of a metered-dose inhaler will not cause a maximal bronchodilatory effect. Both anticholinergic and beta-adrenergic drugs cause dose-dependent bronchodilation when given as aerosols from metered-dose inhalers, and a combination of the two can provide better results. If the response to a single agent is unsatisfactory, use of higher doses is advised and the use of a combination of anticholinergic agents and beta-agonists is recommended. With regard to inhaled corticosteroids, a high dose of inhaled beclomethasone dipropionate (1,500 micrograms per day) can be a effective as oral corticosteroids. Step-by-step pharmacologic therapy with the drugs mentioned above should be used in outpatient management of patients with chronic obstructive pulmonary disease.
Abstract: High doses of inhaled beclomethasone dipropionate (BDP) are effective in some patients with chronic obstructive pulmonary disease (COPD). However, dose-response data for this agent are limited. To determine whether patients receive maximum benefit from 1600 micrograms of BDP, we performed a randomized, double-blind, placebo-controlled, cross-over trial. Twenty-one patients with stable COPD [mean +/- SD: age, 69.1 +/- 6.8 yrs; FEV1, 0.86 +/- 0.28 L] were treated with both inhaled bronchodilators and 1600 micrograms of BDP daily for at least 3 months. Each patient received 30 mg of oral prednisolone or a placebo for 3 weeks. In addition to end-point spirometric assessments daily peak expiratory flow rate, symptom scores, and scores on a chronic respiratory disease questionnaire were recorded for the last week of each 3-week period. Oral prednisolone did not improve FEV1, FVC, symptoms or scores on the questionnaire. We conclude that 1600 micrograms of BDP in addition to inhaled bronchodilators produces maximal improvements in stable patients with COPD.
Abstract: STUDY OBJECTIVE: To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler. DESIGN: Twenty-four male patients with stable COPD (FEV1, 0.96 +/- 0.43 L; 36.8 +/- 17.0 percent predicted [% pred]) completed a randomized, double-blind, placebo-controlled crossover trial with oral theophylline for 4 weeks. MEASUREMENTS AND RESULTS: The average serum theophylline level was 15.0 +/- 5.5 micrograms/mL during treatment. On the whole, without inhalation of bronchodilators, FEV1 was 0.93 +/- 0.42 L during the placebo period and 1.00 +/- 0.43 L (significantly different from placebo; p < 0.01) during the theophylline period. At 15 and 60 min after inhalation of salbutamol, 400 micrograms, and ipratropium, 80 micrograms, the FEV1 with placebo was 1.12 +/- 0.43 L and 1.14 +/- 0.46 L, respectively, and the FEV1 with theophylline was 1.18 +/- 0.45 L (p < 0.01) and 1.20 +/- 0.47 L (p < 0.01), respectively. Daily peak expiratory flow rate also improved. Daily symptom scores were not significantly different between theophylline and placebo periods. Nevertheless, eight patients reported a subjective benefit during the theophylline administration period, and they were thus considered subjective responders. While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders (change in FEV1 between theophylline and placebo treatment 15 min after inhalation, 3.1 %pred; 60 min, 3.5 %pred), postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders (15 min, 1.7 %pred; 60 min, 1.6 %pred). CONCLUSIONS: On the whole, theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD. However, one third of patients with COPD may respond subjectively to theophylline. The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders.
Abstract: Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.
Abstract: The clinical and pathologic features of 46 patients from Japan, Korea, and Taiwan with pulmonary lymphangioleiomyomatosis (LAM) were studied. Only two (5%) among 40 evaluable treatments were assessed to be effective. Some prognostic factors of LAM were recognized. A reduction of the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio was a poor prognostic factor at 2 yr after the first examination, with a statistically significant difference (p < 0.05). An increase in the percentage of predicted total lung capacity (%TLC) correlated with a poor prognosis at 2, 3, and 5 yr after the first examination, with statistically significant differences (p < 0.05). Histologically, two types of pulmonary lesions were observed; a predominantly cystic type and a predominantly muscular type. Patients with predominantly cystic LAM lesions showed a tendency to a poor prognosis from 2 to 5 yr after the biopsy. Among open lung biopsy findings, higher grades of abnormal areas were unfavorable as a prognostic factor from 2 to 5 yr after the biopsy, with statistically significant differences (p < 0.05). Higher grades of cystic lesions correlated inversely with survival at 2, 4, and 5 yr after the lung biopsy, with statistically significant differences (p < 0.05).
Abstract: To study the role of inhaled steroids in treating patients with chronic obstructive pulmonary disease (COPD), 1.6 mg of beclomethasone dipropionate (BDP) were given for 2 weeks after 0.5 mg/kg of oral prednisolone (PSL) for 2 weeks to 43 patients with COPD (mean age 68.7 +/- 5.2 years, mean baseline FEV1, 1.13 +/- 0.44 L). When responders to a corticosteroid (PSL or BDP) were defined as those with a post-steroid EFV1/baseline FEV1 > or = 115% and a post-steroid FEV1-baseline FEV1 > or = 0.2 L, 12 out of 43 patients responded to 30 mg of PSL for 2 weeks and 13 responded to 1.6 mg of BDP for 2 weeks. We considered those 17 patients who responded to 2 weeks of PSL or 2 weeks of BDP or both, to be possible steroid responders, and they continued inhaling BDP for 4 more weeks. In 8 of these 17 patients (19%), FEV1 had increased by the end of the 6 weeks. Inhaled BDP was considered useful in treating some patients with COPD.
Abstract: To study the effects of an inhaled steroid on airway hyperresponsiveness (AHR) in chronic stable asthma, AHR was measured every month for 1 year in seven patients after their asthma had stabilized, i.e., when they had no wheezing or dyspnea, and their peak expiratory flow rates (PEFR) were at least 80 percent of the highest value. During the study period, no patient wheezed or had dyspnea, and daily variation in PEFR was less than 20 percent. In six patients, FEV1 was stable, and PEFR was always at least 80 percent of the highest value. AHR became less severe, by a factor of at least 2, in five of these six patients, but one patient's condition did not improve. The one patient whose PEFR fell below 80 percent of the highest value had more than a 4-fold increase in the severity of AHR. In conclusion, the severity of AHR can be reduced, even in patients with chronic stable asthma, if daily PEFR can be maintained in an optimal range by long-term use of inhaled corticosteroids.
Abstract: We studied the clinical features of 17 Japanese patients with pulmonary eosinophilic granuloma. Fourteen of the patients were men and three were women; they ranged in age from 19 to 64 years, with a mean of 34 years at the time of the first examination. Pathologic diagnosis in all patients was based on histologic findings of specimens obtained by open lung biopsy. Major symptoms were dry or productive cough, chest pain, dyspnea, and fever; 23.3% of the patients were asymptomatic. Five patients had pneumothorax. Most patients did not have abnormal physical signs. All 17 patients had histories of smoking, and 14 had started to smoke cigaretts before the age of 20 years. Ten patients (58.8%) first presented with cough or dyspnea, and in the other patients (41.2%) the first abnormalities detected were pulmonary infiltrates on chest radiographs during health examinations. Chest roentgenograms usually showed bilateral abnormalities. These abnormalities were distributed over all lung fields in 9 cases (52.9%), in the upper and middle lung fields in 4 cases (23.5%) in the upper lung fields in 3 cases (17.7%), and in the middle lung fields in 1 case (5.9%). Micronodular, reticular, cystic or linear shadows were evident in most cases, and were mixed in various proportions. Eleven patients (65%) had abnormalities of pulmonary function. Low %VC and %FEV1 and high RV/TLC ratios were observed in 20-40% of the patients. Low DLCOs (%DLCO < 70%) were observed in 53% of the patients. Arterial blood gases were normal in 11 of 15 patients. The extent of shadows in the chest roentgenogram was related to the frequency of dyspnea, to the total number of cells in bronchoalveolar lavage fluid, and to the abnormally low %FVC and %FEV1, but not to the %DLCO. Data from bronchoalveolor lavage fluid were non-specific in this disease, but further studies will be needed. Follow-up data were collected on 16 patients. The mean time from the histologic diagnosis after open lung biopsy to the last observation was 81.8 +/- 45.1 months (range, 2 months to 15 years). One patient died of pulmonary eosinophilic granuloma. The usefulness of steroid therapy remains uncertain.
Abstract: In CT the presence of mediastinal or hilar lymphadenopathies and thickened bronchovascular bundles are landmarks for the diagnosis of pulmonary sarcoidosis. The major CT findings for parenchymal involvement are thickened bronchovascular bundles, large parenchymal nodules, pleural or subpleural nodules, ground-glass opacities, local lung volume loss (distortion of the lung parenchyma), and microscopic and macroscopic honeycombing. The thickened bronchovascular bundles correspond histologically to granulomas, either with or without perigranulomatous fibrosis in the connective tissue sheath around the pulmonary vessels and airways. Conglomerate granulomas are represented on CT by high-attenuation nodules, and the ground-glass opacities are caused by the summation of a number of small granulomas in the interstitium.
Abstract: The clinical features of 68 Japanese patients (53 men and 15 women; mean age 44 years) with primary pulmonary alveolar proteinosis were reviewed. Pulmonary alveolar proteinosis was diagnosed from histologic findings after open lung biopsy (n = 7) or transbronchial lung biopsy (n = 61). Major symptoms were a dry cough (24.2%) and dyspnea or shortness of breath on exertion (51.5%), but one third of the patients were asymptomatic. Crackles were audible in 30% of the patients, but clubbing (6%) and cyanosis (4%) were rare. Ten patients had been occupationally exposed to dust. Slightly less than half (46%) of the patients first presented with symptoms, and the remainder (54%) first presented with abnormal pulmonary infiltrates seen on chest roentgenograms taken during general health examinations. Many patients had abnormally high levels of LDH and CEA in serum (62% and 63%, respectively). Restrictive pulmonary dysfunction (%VC < 80%) was seen in 31% of the patients, an abnormally low DLco (%DLco < 70%) was seen in 62%,m and hypoxemia (PaO2 < 80 mmHg) was seen in 67%. Arterial blood gas tension was closely correlated with the severity of disease in these patients. Chest roentgenograms usually showed bilateral symmetric alveolar infiltrates, mainly distributed from hilar areas toward the pleura, but on CT scans many of the shadows were mixed with alveolar and interstitial infiltrates of various extent along the pulmonary arteries and bronchi. There was no apparent relation between chest roentgenographic findings and chest CT findings in these patients. Neither the extension nor other characteristics of shadows in the chest roentgenograms and chest CT scans were closely related to symptoms, laboratory data, or pulmonary function in these patients. Symptoms were alleviated and chest roentgenographic findings improved in 82% of the 51 patients who underwent therapeutic bronchoalveolar lavage, and in 94% of the 17 patients who did not undergo that procedure. In patients who underwent therapeutic bronchoalveolar lavage and also in those who recovered spontaneously, both diffusing capacity and blood gas values improved significantly. When compared to the patients who did not undergo therapeutic bronchoalveolar lavage, significantly more of those who did undergo that procedure has initial PaO2 values below 60 mmHg, and fewer of them had values greater than 80 mmHg. Thus, a PaO2 below 60 mmHg may be an indication for therapeutic bronchoalveolar lavage in patients with this disease. During the follow-up period (mean 5 years, range 2 months to 23 years), four patients had pneumothorax and none died of pulmonary alveolar proteinosis.
Abstract: BACKGROUND--Inhaled anticholinergics and beta agonists are widely used in the treatment of patients with chronic obstructive pulmonary disease (COPD). However, dosage requirements have not been thoroughly evaluated and comparative dose-response data for these agents are limited. METHODS--Twenty men with stable COPD of mean (SD) age 69.4 (5.8) years and FEV1 0.93 (0.38) litres were studied in randomised, double blind, crossover, placebo controlled experiments. All of the patients received two, four, eight, and 16 puffs of ipratropium bromide (20 micrograms/puff), flutropium bromide (30 micrograms/puff), oxitropium bromide (100 micrograms/puff), fenoterol (200 micrograms/puff), or placebo in random order on five separate days. Doses were administered by a metered dose inhaler at intervals of 60 minutes to give cumulative doses of two, six, 14, and 30 puffs. Five mg of nebulised salbutamol was administered 60 minutes after the patient had received the final 16 puffs of each regimen. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), heart rate, and blood pressure were measured five minutes before each treatment and 30 minutes after treatment with nebulised salbutamol. RESULTS--FEV1 and FVC reached a plateau after administration of a cumulative dose of 14 puffs of ipratropium bromide (280 micrograms) or flutropium bromide (420 micrograms), and after six puffs of oxitropium bromide (600 micrograms). There were no differences with respect to maximum increases in FEV1 and FVC amongst the three anticholinergic agents. However, after six puffs oxitropium bromide produced a greater increase in FEV1 than either ipratropium bromide or flutropium bromide. Fenoterol caused a greater increase in both FEV1 and FVC than the three anticholinergic agents after six puffs, as well as a greater increase in pulse rate. Oxitropium bromide produced a greater increase in pulse rate than the other anticholinergics after 14 puffs. The incidence of side effects was dose-related and notable adverse effects were reported after 30 puffs of ipratropium bromide, 14 puffs of oxitropium bromide, and two puffs of fenoterol. CONCLUSIONS--Oxitropium bromide produced a greater bronchodilator effect than either ipratropium bromide or flutropium bromide when used at doses of less than six puffs, without apparent side effects. There were, however, no differences in maximal response between these drugs. Fenoterol may have a greater peak bronchodilator effect than the anticholinergic agents but it causes more adverse effects, even at lower doses. Depending upon the balance between efficacy and side effects, oxitropium bromide may be preferred in the treatment of patients with COPD.
Abstract: Inhaled anticholinergics may be the first-line therapy for stable COPD. However, the effect of inhaled anticholinergic agents on exercise capacity is still controversial. Fourteen patients with stable COPD (age, 64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial. All the patients were studied by symptom-limited progressive cycle ergometry before and 90 min after the inhalation of either oxitropium bromide, 800 micrograms, or an identical placebo. Spirometry was assessed before and after each exercise test. While FEV1 averaged 0.85 +/- 0.34 L at 90 min after the inhalation of placebo, FEV1 was 1.01 +/- 0.41 L at 90 min after the inhalation of oxitropium, 800 micrograms (significant from placebo, p < 0.001). The maximal workload of 94.0 +/- 25.8 W after oxitropium administration was significantly greater than the 87.6 +/- 24.7 W measured after placebo (p < 0.01). The maximal minute ventilation was 40.2 +/- 12.3 L/min after oxitropium inhalation and 36.8 +/- 10.5 after placebo inhalation (p < 0.05). The differences in maximal oxygen consumption, maximal carbon dioxide production, and maximal heart rate between oxitropium and placebo inhalation also were statistically significant (p < 0.05, p < 0.05, and p < 0.01, respectively). There was a significant correlation between the change in maximal workload and the change in FEV1 before and after inhalation (r = 0.625, p < 0.01). The inhalation of oxitropium bromide, 800 micrograms, can improve the exercise capacity of patients with stable COPD. It is suggested that the effect is due to the bronchodilation induced by this drug.
Abstract: We developed an automated method to recognize the lung in a computed tomographic (CT) image. With computer-assisted analysis, we were able to describe the continuous low attenuation (less than -960 Hounsfield units) areas (CLA) on chest CT scans. The size (CLAs) and number (CLAn) of the CLA and the percentage of total lung area occupied by low attenuation area (LAA%) were measured using CT scans obtained from 24 patients with chronic pulmonary emphysema (CPE) and 13 control patients. The automated algorithm recognized the lung areas successfully in all patients. The CLAs and LAA% were significantly higher, and CLAn was significantly lower in patients with CPE than in controls. There was a significant correlation between CT parameters and pulmonary function test results. The histograms of the size of CLA could be represented as a power function in each patient. This automated method should be useful in objectively defining the affected areas in the lungs of patients with CPE.
Abstract: The present paper reports theoretical equations for the predictive performance of the Bayesian forecasting method. The precision of parameter estimates and predicted concentrations for an individual was described by general equations with the aid of a variance-covariance matrix of parameter estimates that involved the Bayes theorem. The equations were applied to assess the predictive performance of the one-point Bayesian method in association with blood sampling time, the population parameters, and the pharmacostatistical model. The simulation study showed that the prediction error in parameter estimates essentially depended upon the sampling time but the magnitude of dependency was affected by the size of inter- and intraindividual variances. With a smaller value of interindividual variance, the dependency on sampling time was less apparent. Effects of sampling time were further examined using clinical data obtained from 20 patients taking theophylline, and the results were in good agreement with the theoretical consideration. The present general equations are useful to investigate the sampling strategy as well as structural and variance modeling on the predictive performance of the Bayesian method.
Abstract: To investigate the relationship between the emphysematous changes and bronchodilator responses in patients with chronic airflow obstruction (CAO), we studied the correlation between bronchodilator response to 10 mg inhaled metaproterenol and the extent of emphysema, using selective alveolobronchogram (SAB). Fifty-one patients with CAO were classified into 3 groups by the extent of emphysematous changes detected by SAB. In group 1, no or mild emphysematous change was observed on SAB (n = 9); in group 2, there were significant emphysematous changes but the involved area was less than 75% (n = 17); in group 3, emphysematous change was extensive and covered more than 75% (n = 25). The post-bronchodilator forced expiratory volume in 1 sec (FEV1) of patients in group 3 was significantly lower than in groups 1 and 2. The mean value of changes of FEV1 as a percentage of predicted FEV1 of patients in group 3 was significantly lower than in groups 1 and 2. These results indicated that the extent of emphysematous change correlated positively with the severity of fixed airflow obstruction, and negatively with the bronchodilator response.
Abstract: BACKGROUND--Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS--Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS--Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS--The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.
Abstract: In our study of 52 patients with idiopathic pulmonary fibrosis (IPF), we found that the incidence of clubbing of the fingers was significantly more frequent in male than in female patients and in patients who showed lesser grades of honeycombing and higher grades of smooth-muscle proliferation in the pulmonary fibrotic changes (p < 0.01). Smooth-muscle proliferation in fibrotic changes of open lung biopsy specimens correlated with the mode of detection of IPF and the presence of clubbing of the fingers, duration of symptoms of the lower respiratory tract, and a higher extent of pulmonary infiltrates on chest radiographs (p < 0.05). However, the presence of clubbing of the fingers or grades of smooth-muscle proliferation in the pulmonary fibrotic changes did not correlate with the 2-year survival after open lung biopsy.
Abstract: The population pharmacokinetics of theophylline were studied in 55 patients with stable chronic airway obstruction. Two hundred and seventy six theophylline serum concentrations after intravenous short infusion were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, smoking habit, age and the measurement of arterial blood gases (oxygen tension: PaO2, carbon dioxide tension: PaCO2, blood pH) and clinical laboratory tests (serum albumin concentration, haematocrit) on the pharmacokinetic parameters of theophylline was examined by the likelihood ratio test. Assessment of each factor was made by a forward selection method. In the final regression model, the total body clearance (CL, l/h/kg) was related to the value of PaCO2 as well as to the presence of hepatic dysfunction, and the volume of distribution (Vd, l/kg) was related with the PaCO2 value as expressed in the following equations: CL = exp(-3.78 - 0.525.HF + 0.0233.PaCO2) and Vd = exp(-1.12 + 0.00934.PaCO2), where HF is a categorical variable with a value of unity if a patient has hepatic dysfunction otherwise zero. The interactions among blood gas measurements were observed and the CL and Vd of theophylline would be inversely correlated with PaO2 or pH, if we selected PaO2 or blood pH to be a more important factor than PaCO2. The inter-individual variabilities in CL and Vd were 38.5% and 12.5%, respectively, and the residual variability in theophylline serum concentrations was 10.6% as a coefficient of variation. This final model and the population parameters of theophylline will be useful for individualization of a drug dosage regimen by means of the Bayesian method.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: To investigate the additive effect of oral theophylline on combined inhaled anticholinergic agent and beta 2-agonist therapy, 12 patients with stable COPD (64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial of oral theophylline for a 4-week period (400 mg for 2 weeks, followed by 600 mg for 2 weeks). All of the patients continued to inhale both salbutamol, 200 micrograms, and ipratropium bromide, 40 micrograms, using a metered-dose inhaler four times a day. Spirometry was assessed before, and 15 and 60 min after the inhalation of bronchodilators at 2-week intervals. Even after the inhalation of salbutamol and ipratropium, theophylline significantly improved FEV1 and daily peak expiratory flow rate compared with the placebo. No significant improvement in the daily symptom scores for cough, sputum, wheezing, or shortness of breath was observed throughout the different phases of treatment. This study shows that the additive bronchodilating effect of theophylline, when used in combination with salbutamol, 200 micrograms, and ipratropium, 40 micrograms, is significant but small in stable COPD. The addition of theophylline did not significantly improve the patient's symptoms. Oral theophylline, when used in combination with an inhaled anticholinergic agent and an inhaled beta 2-agonist, may be of limited value in the treatment of stable COPD.
Abstract: High-resolution computed tomography (HRCT) allows accurate assessment of the pattern and distribution of diffuse lung diseases. Optimal interpretation of the HRCT images requires understanding of some basic concepts of normal anatomy, as well as the pathologic basis for the HRCT findings in diffuse lung disease. This review summarizes our experience with over 400 radiologic-pathologic correlations in diffuse lung disease. These correlations include contact radiography with stereo views and stereomicroscopic images of lung specimens. We describe our technique to inflate and fix the lung specimens and illustrate normal and abnormal lung morphology.
Abstract: The purpose of this study was to evaluate the role of high-resolution computed tomography (HRCT) in the clinical diagnosis of diffuse infiltrative lung disease (DILD). Diagnostic accuracy was compared using both chest radiography and HRCT. One hundred thirty-four cases of DILD, representing 21 different diseases, were selected for study, and the disease state was confirmed either histologically or microbiologically. The HRCT images and chest radiographs, available in all cases, were reviewed separately and in random order by 20 physicians who were provided only with information on each patient's age and sex. Overall, a correct first-choice diagnosis was made in 38 percent using radiographs and in 46 percent using HRCT images (p < 0.01). The correct diagnosis was among the top three choices in 49 percent when chest radiographs were used, and in 59 percent when HRCT images were viewed (p < 0.01). The correct first-choice diagnosis increased remarkably when the HRCT was used in usual interstitial pneumonia, sarcoidosis, alveolar proteinosis, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis, and pulmonary lymphangiomyomatosis. High-resolution computed tomography was confirmed to be superior to conventional radiography in the accurate diagnosis of DILD in clinical practice.
Abstract: PURPOSE: Computed tomographic (CT) findings of pulmonary sarcoidosis were correlated with histopathologic features determined at open lung biopsy or autopsy. MATERIALS AND METHODS: Eight patients (six men and two women, aged 22-65 years) with pulmonary sarcoidosis diagnosed at histologic examination were studied at CT with a high-spatial-frequency algorithm. RESULTS: The most frequent CT features were irregularly thickened bronchovascular bundles (seven of eight cases [88%]) and small nodules along vessels (four cases [50%]). These features corresponded to granulomas formed in the connective tissue sheath around the pulmonary vessels and airways. This characteristic CT appearance was the result of the bronchovascular distribution of sarcoid granulomas. Granulomas adjacent to the visceral pleura or formed in the pleura in four patients were correlated with pleural or subpleural involvement. Ground-glass attenuation, present in six patients (75%), did not correlate with alveolitis in any patient. CONCLUSION: CT is a valuable technique with which to visualize the characteristic location of sarcoid granulomas in the pulmonary parenchyma.
Abstract: Oxitropium bromide is a novel anticholinergic bronchodilator agent. The purpose of this study was to compare the bronchodilating and cardiovascular effects of oxitropium (0.2 mg), fenoterol (0.4 mg), combined oxitropium and fenoterol (0.2 mg and 0.4 mg, respectively) over a 10-h test period. Fourteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 0.95 +/- 0.38L) were studied in a randomized, double-blind, placebo-controlled trial. Combined oxitropium and fenoterol produced significantly greater improvements in FEV1 over a time span of 15 min to 10 h and in the area under the time-FEV1 curve (AUC) than either oxitropium or fenoterol alone. The effects of oxitropium on both FEV1 and AUC values were similar to those of fenoterol. Oxitropium resulted in a greater increase in FEV1 than the placebo even after 10 h. In contrast; fenoterol produced a significant improvement in the FEV1 for only 15 min to 4 h. Oxitropium showed no adverse cardiovascular effects, whereas fenoterol was associated with an increased heart rate at 15 min and 1 h after the administration. We conclude that oxitropium bromide is an effective and safe bronchodilator for even elderly patients with COPD.
Abstract: The authors reviewed 46 cases of idiopathic pulmonary fibrosis with usual interstitial pneumonia (UIP), correlating findings on high-resolution computed tomographic (HRCT) scans with findings in specimens obtained at open lung biopsy and autopsy. The following HRCT findings were observed: (a) an accumulation of small cystic spaces with thick walls, (b) air bronchiolograms within areas of intense lung attenuation, (c) rugged pleural surfaces, (d) irregularly thickened pulmonary vessels, (e) bronchial wall thickening, and (f) slightly increased lung attenuation. Macroscopic honeycombing correlating with small cystic spaces was demonstrated at HRCT and pathologic examination. Air bronchiolograms in the areas of intense lung attenuation (ie, microscopic honeycombing) corresponded to dilated bronchioles (greater than 1 mm in diameter) with fibrosis. Irregularly thickened vessels and bronchial walls and irregular pleural surfaces were the result of fibrosis in the periphery of the secondary pulmonary lobules. Areas of slightly increased lung attenuation seen on the HRCT scans correlated with patchy alveolar septal fibrosis or inflammation. The authors conclude that microscopic honeycombing and a perilobular distribution in UIP may be clearly identified with HRCT.
Abstract: The purpose of this study was to establish the optimal bronchodilating drug among therapies currently available for clinical treatment of the stable phase of chronic obstructive pulmonary disease (COPD). The efficacy of ipratropium bromide 40 micrograms, salbutamol 200 micrograms, and ipratropium bromide 40 micrograms plus salbutamol 200 micrograms was compared in 14 patients with COPD. Daily PEFR was obtained during the last seven days of a 2 week period incorporating drug inhalation four times daily. FEV1 and FVC were assessed on the final day of the treatment period. In the absence of bronchodilating medication, FEV1 was 1.27 +/- 0.13 l (52.9 +/- 5.1% pred). With ipratropium bromide 40 micrograms alone, FEV1 was 1.43 +/- 0.13 l (59.8 +/- 5.3% pred). A similar value was obtained for salbutamol 200 micrograms: 1.45 +/- 0.14 l (61.0 +/- 5.4% pred). However, FEV1 following the administration of ipratropium bromide 40 micrograms in combination with salbutamol 200 micrograms was 1.51 +/- 0.13 l (63.6 +/- 5.3% pred). The percent increase in FEV1 (compared to the value obtained without medication) was significantly higher with combined ipratropium bromide 40 micrograms plus salbutamol 200 micrograms (122.2 +/- 3.8%) than with either ipratropium bromide 40 micrograms (114.8 +/- 5.5%) or salbutamol 200 micrograms (116.5 +/- 4.4%) alone. Furthermore, the daily post-dilator PEFR improved significantly more with the combined therapy four times a day (311 +/- 29 l/min) than with either ipratropium bromide 40 micrograms (296 +/- 30 l/min) or salbutamol 200 micrograms (303 +/- 29 l/min) therapy alone. There was no discernible difference between results obtained with ipratropium bromide 40 micrograms versus salbutamol 200 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The phase difference (PD) between mouth flow and chest flow during rest breathing was measured in pulmonary diseased patients using a body box and the results were compared with normal subjects. Whereas the PD increased in patients with chronic pulmonary obstructive disease (COPD) compared to normal subjects, PD was found to be normal in patients with interstitial pulmonary fibrosis (IPF) (Normal: 2.94 +/- 1.25, COPD: 11.32 +/- 4.17*, IPF: 2.62 +/- 1.67 degrees; *P < 0.01). PD correlated well with FEV1.0/VC%, PFR, RV/TLC, VTG and Ra (r: -0.759, -0.672, -0.788, 0.666, 0.606). From an in-depth analysis of the results, we suggest that the factors which increase PD in COPD patients include hyperinflation of the lung, increases in airway resistance and increases in the parallel inhomogeneity of airway resistance accompanied by an unevenness of alveolar pressures. PD was thought to be clinically useful for the evaluation of the pathological stages of COPD because it reflects the overall clinical manifestations in COPD patients.
Abstract: We studied the effect of 30 mg of prednisolone on 29 Japanese patients with chronic obstructive pulmonary disease (COPD). The mean value of the baseline forced expiratory volume in one second (FEV1; mean +/- SEM) was 1.14 +/- 0.12 l (46.9 +/- 3.9% pred) and the FEV1 following the steroid trial was 1.30 +/- 0.12 l (53.7 +/- 4.3% pred). Post-trial FEV1--baseline FEV1/predicted FEV1 was 6.8 +/- 1.9%. Five patients (17%) had more than a 15% increase in FEV1 as a percentage of predicted FEV1. Post-trial FEV1/baseline FEV1 was 117.3 +/- 4.3%, and 12 patients (41%) had more than a 20% increase in FEV1 after the trial. Acute bronchodilator response to beta-agonist correlated positively with the response to corticosteroid. Baseline spirometries, blood eosinophil counts, serum IgE levels, sputum eosinophil counts, family history of asthma, and history of paroxysmal dyspnea did not vary across responders and non-responders. Patients with severe COPD should be treated to achieve the best possible pulmonary functions indicated by a steroid trial within the limit of acceptable levels of adverse effects.
Abstract: A 58-year-old man with history of productive cough and mild exertional dyspnea for several years was admitted to our hospital because of abnormal shadow on chest radiograph. Bronchofiberscopic examination revealed a polypoid tumor almost completely obstructing the right main bronchus. Bronchoscopic biopsy specimens showed amyloid-like deposits in the connective tissue surrounded by epithelium-like tumor cells with squamous metaplasia, but no diagnostic findings. Malignant tumor was suspected and right upper lobectomy was performed. The surgical specimen revealed nests of tumor cells surrounded by amorphous eosinophilic substance, which was confirmed to include amyloid fibrils by electron microscopy. A few tumor cells contained argyrophil granules by Grimelius staining, and some showed PAP staining for calcitonin. There was no evidence of involvement of other organs including the thyroid gland during the four year postoperative follow-up period. This case was diagnosed as thyroid medullary carcinoma-like tumor of the lung, which is a bronchopulmonary carcinoid-related tumor.
Abstract: The clinical features of 34 Japanese patients with bronchiolitis obliterans organizing pneumonia (BOOP) are discussed. Thirty-two patients (94 percent) had symptoms of cough, fever, or dyspnea. On chest roentgenograms, bilateral patchy infiltrates were seen most frequently in 23 patients (68 percent), followed by small linear opacities in five (15 percent), both patchy infiltrates and reticulonodular opacities in four (12 percent), and reticulonodular opacities in two (6 percent). The bronchoalveolar lavage fluid (BALF) cell findings obtained from 26 patients revealed an increase in the percentage of lymphocytes in 20 patients (77 percent), neutrophils in 15 (58 percent), and eosinophils in 16 (62 percent), and a decrease in the CD4+/CD8+ ratio in 14 of 23 patients (61 percent). Corticosteroids were administered to 25 patients. Except for one patient who died, the prognosis was good in all patients. Further, in patients without corticosteroid therapy, the prognosis was good.
Abstract: Diffuse panbronchiolitis (DPB) is characterized by chronic airflow limitation and airway inflammation with bronchiolar lesions. Chest radiographs of patients with DPB usually show small nodular shadows throughout both lungs. The authors investigated the nature and pathogenesis of the radiologic features of DPB by correlating high-resolution computed tomographic (HRCT) findings with histopathologic features. The HRCT images of nine patients with DPB were compared with the observations made with inflated lung specimens. The HRCT findings of DPB included centrilobularly distributed, small rounded areas of attenuation; branched linear areas of attenuation, contiguous with the small rounded areas; dilated airways with thick walls, also common outside secondary pulmonary lobules; and decreased lung attenuation in peripheral areas due to air trapping caused by bronchiolar narrowing in the subpleural zones. The authors believe that HRCT best demonstrates this characteristic location of small rounded areas of attenuation associated with dilated airways.
Abstract: The factors which increase phase differences between mouth flow and chest flow in patients with obstructive disorders were analyzed. From airway resistance, thoracic gas volume and measured chest flow, phase difference was predicted by the Runge-Kutta (R.K.) method assuming respiratory system to be a single compartment model. The ratio of the measured phase differences to the predicted value by the R.K. method in normal subjects was 0.99 +/- 0.25. These results suggest that a single compartment model can be applied to normal respiratory system. In contrast, predicted phase differences were remarkably higher than measured values in patients with obstructive disorders (CPE: 1.83 +/- 0.63, DPB: 1.50 +/- 0.48). This phenomenon could be explained by the existence of parallel inhomogeneity of alveolar pressure.
Abstract: The phase difference between mouth flow and chest flow in cases of pulmonary diseases measured using a body box was compared with those in normal subjects. Phase differences in chronic pulmonary emphysema (CPE) and diffuse panbronchiolitis (DPB) patients increased compared to normal subjects, but remained normal in interstitial pneumonitis patients (Normal: 3.76 +/- 1.71, CPE: 10.70 +/- 4.93, DPB: 10.81 +/- 3.15, IP: 3.83 +/- 0.15 degrees). In addition, there was a good correlation with FEV1.0, FEV1.0% and RV/TLC (r: -0.634, -0.610 and 0.803). The analysis of phase differences during rest breathing is clinically useful because it is non-effort dependent and can evaluate the degree of airway disorders.
Abstract: Diffuse panbronchiolitis (DPB) is a disease characterized clinically by chronic airflow limitation, therefore patients with DPB are frequently treated with bronchodilators. However, there have been no reports on bronchodilator effects in patients with DPB. Because bronchodilator effects can be influenced by low baseline level of pulmonary function, we evaluated acute responses to inhaled metaproterenol (10 mg) in 31 patients with DPB and in 40 patients with pulmonary emphysema. Patients of both groups were clinically diagnosed, and, in addition, by usage of high-resolution computed tomography. All the subjects in both groups had a post-bronchodilator FEV1/FVC less than 0.7. There was no difference in baseline FEV1 between either group; FEV1 was 1.24 +/- 0.64 l (47.1 +/- 17.8% pred) in DPB vs. 1.24 +/- 0.64 l (51.0 +/- 19.0% pred) in pulmonary emphysema. Two indices, post FEV1/pre FEV1 and post FEV1-pre FEV1/predicted FEV1, were used for the judgement of bronchodilator response. Post FEV1/pre FEV1 was 110.3 +/- 9.3% in DPB and 119.9 +/- 17.1% in pulmonary emphysema. Post FEV1-pre FEV1/predicted FEV1 was 4.5 +/- 4.2% in DPB and 8.6 +/- 6.2% in pulmonary emphysema. Bronchodilator responses for both indices was larger in pulmonary emphysema than in DPB (both, p less than 0.01). It has been reported that post FEV1/pre FEV1 correlates negatively to baseline FEV1 and that post FEV1-pre FEV1/predicted FEV1 is positively correlated to baseline FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The X-ray CT findings of two cases of pulmonary lymphangioleiomyomatosis were reported. The correlation between high-resolution CT findings and inflated biopsy specimens was studied. The X-ray CT findings are 1) multiple low attenuation areas, 2) diffuse areas of slightly increased density and 3) irregular enlargement of pulmonary vascular images. Each low attenuation are turned out to correspond to emphysematous lesions. Slightly increased densities on CT images seemed to be caused by a summation of many small nodules of a proliferation of smooth muscle cells located in the wall of respiratory bronchioles and alveolar ducts, with or without intraalveolar hemosiderosis. Some nodular lesions in bronchiolar walls were so close to neighboring vessels that they could not be separated from vascular images on CT, so peripheral vascular images were irregularly thickened. X-ray CT reflected more actual pathological findings than routine chest radiographs. As low attenuation areas on CT images have been reported to be representative of pulmonary emphysema, it is thought that the above CT findings must be differentiated from those of pulmonary emphysema. While pulmonary vascular images were thin and stretched on the CT in patients with emphysema, they were irregularly thickened on the CT of patients with LAM. Furthermore, while CT of emphysema often revealed overinflation or decreased density, diffuse areas of slightly increased density were never found in emphysema.
Abstract: We studied CT-pathologic correlations of diffuse panbronchiolitis. The CT images of five DPB patients were compared with inflated lung specimens taken from three open lung biopsy, one lobectomy and one autopsy. The specimens were observed using a stereomicroscope, contact radiographs and histological section. All cases were diagnosed histologically by the presence of unit lesion of panbronchiolitis. The CT findings of DPB were: 1. diffuse small rounded and linear opacities, 2. dilation of small bronchi and bronchioles, 3. bronchial wall thickening. Because small rounded opacities on the CT images were usually separated from the pleura and PV shadows (the edge of secondary lobules) as a constant distance (2 to 3 mm), they were distributed in centrilobular regions. They corresponded to the collection of foamy histiocytes and lymphoid cells, where the unit lesion of panbronchiolitis were included. Although peripheral airways could never be seen in normal CT images, small linear opacities or enlarged peripheral vascular opacities just continuous with small rounded opacities corresponded to bronchioles dilated with intrabronchial secretion. In addition, peripheral airways were sometime seen to be dilated in CT images. Cylindrical airway dilation was more prominent in the peripheral portion of airways in both CT images and lung specimens. Thickening of bronchial wall observed in CT of a case could not be confirmed in lung specimen, in which probably intrabronchial secretion might contribute to bronchial wall thickening. From the viewpoint of diagnosis, the problem is that small nodular shadows are too large to show respiratory bronchiolitis itself. Moreover, because bronchiectasis is often found in the cases of DPB, the relationship between DPB and other causes of bronchiectasis should be evaluated.
Abstract: It is possible to differentiate to some degree to bronchiolitis obliterans organizing pneumonia (BOOP) of unknown etiology from idiopathic usual interstitial pneumonia (UIP) on the basis of clinical symptoms, chest X-ray findings, pulmonary function test and blood gas findings, but in certain patients it can be difficult. Cell findings in bronchoalveolar lavage fluids (BALF) were compared between 8 patients with BOOP and 28 patients with UIP, both diagnosed histologically by open lung biopsy. Findings characteristic of BOOP included (1) an increase in the percentage of lymphocytes, (2) an increase in the percentage of eosinophils, and (3) a decrease in the OKT4+/OKT8+ ratio. These findings provide useful information in making a clinical diagnosis of BOOP and in evaluating proper steroid treatment in patients who unable to undergo open lung biopsy.
Abstract: Though bronchiolitis obliterans organizing pneumonia (BOOP) was proposed as a new infiltrative lung disease in 1985, we think it has two radiologic problems. First, in spite of interstitial pneumonia, about half of chest radiographs of BOOP has been reported to show alveolar opacities. Second, because radiologic features of both some cases of BOOP and of usual interstitial pneumonia (UIP) show reticular shadows on chest radiographs, it is sometimes difficult to differentiate between two diseases. We correlated CT images with open lung biopsy specimens and evaluated CT's ability to differentiate BOOP from UIP. CT findings of all cases of BOOP were: (1) markedly increased dense infiltrates of various sizes which demarcated sharply from normal lung field. Air bronchogram was always present. (2) less dense images were seen which also stood out against the normal lung field. The former corresponded to air space consolidation formed by organized exudates and inflammatory cells within alveolar ducts and alveoli, while the latter indicated luminal and mural alveolitis. Both findings were sharply delineated from each other probably because of intervening interlobular septa. Conglomerated small cystic shadows and air bronchography within areas of intense lung density were seen in CT images of most of 28 patients with UIP. Those findings proved to correspond to macroscopic or microscopic honey combing which were not seen in our cases of BOOP. These radiologic and pathologic features of UIP were different.
Abstract: A sensitive and highly specific method for the determination of theophylline in serum by high-performance liquid chromatography (HPLC) has been developed. Theophylline was completely separated from paraxanthine, a major metabolite of caffeine which has been known to interfere with most isocratic reversed-phase HPLC methods, with a mixture of acetonitrile/tetrahydrofuran/acetate buffer (10 mM, pH 5.0; 5:1:94, v/v %) as the mobile phase using a C18 bonded reversed-phase column. Neither the other xanthine and uric acid derivatives nor numerous drugs tested were found to interfere. The proposed method was applied to therapeutic monitoring utilizing its excellent precision, reproducibility and high specificity for theophylline.
Abstract: Positron emission tomography with radioactive nitrogen gas as well as CT were performed in seven patients with diffuse panbronchiolitis (DPB) to evaluate regional changes on pulmonary ventilation and lung attenuation values. Special focus of this study was on the difference between the central and peripheral parts of the lung. Mean ventilatory time constants measured in the peripheral parts of the lung were significantly greater than those in the central parts. Moreover, mean CT attenuation values in the peripheral parts were also significantly lower than those in the central parts, indicating that hyperinflation of the lung in DPB was located mainly in the peripheral parts. Such stratified distribution of ventilatory impairment is considered to be characteristic of diffuse bronchiolar narrowing because, in the peripheral parts of the lung, there are no large airways. In addition, different branching patterns of airways between the central and peripheral parts of the lung may play an important role in the mechanism of selective injury of bronchioles in the peripheral parts.
Abstract: Morphologic changes and ventilation abnormalities in the lung that resulted in the peripheral perfusion stripe (the stripe sign) on pulmonary perfusion scintigrams were studied in six patients. Chest radiographs, computed tomography (CT) scans, and positron emission tomography (PET) scans obtained using N-13 were compared. Although there was no apparent correlation between the presence of the stripe sign and the findings on the chest radiographs, PET scans depicted ventilation abnormalities in all of 11 lung areas with the stripe sign in six patients. In addition, ventilation was affected more severely in the central part of the lung than in the subpleural region in ten of the 11 lung areas. CT scans demonstrated emphysematous changes, with low attenuation values located mainly in the central part of the lung in all four patients examined. The results suggest an intimate relationship between the stripe sign and the central pattern of pulmonary emphysema.
