[Show abstract][Hide abstract] ABSTRACT: Although the rate of annual decline in FEV1 is one of the most important outcome measures in chronic obstructive pulmonary disease (COPD), little is known about intersubject variability based on clinical phenotypes.
To examine the intersubject variability in a 5-year observational cohort study, particularly focusing on emphysema severity.
A total of 279 eligible patients with COPD (stages I-IV: 26, 45, 24, and 5%) participated. We conducted a detailed assessment of pulmonary function and computed tomography (CT) at baseline, and performed spirometry every 6 months before and after inhalation of bronchodilator. Smoking status, exacerbation, and pharmacotherapy were carefully monitored. Emphysema severity was evaluated by CT and annual measurements of carbon monoxide transfer coefficient.
Using mixed effects model analysis, the annual decline in post-bronchodilator FEV1 was -32±24 (SD) ml/yr (n=261). We classified the subjects of less than the 25th percentile as Rapid decliners, the 25th to 75th percentile as Slow decliners, and greater than the 75th percentile as Sustainers (-63±2, -31±1, and -2±1 [SE] ml/yr). Emphysema severity, but not %FEV1, showed significant differences among the three groups. Multiple logistic regression analysis demonstrated that the Rapid decliners were independently associated with emphysema severity assessed either by CT or carbon monoxide transfer coefficient. The Sustainers displayed less emphysema and higher levels of circulating eosinophils.
Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers and Rapid decliners warrant specific attention in clinical practice.
American Journal of Respiratory and Critical Care Medicine 01/2012; 185(1):44-52. DOI:10.1164/rccm.201106-0992OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 50-year-old man was referred and admitted to our hospital because of pneumonia and pleuritis. The patient had attempted suicide by inhaling automobile exhaust 3 years ago. Carbon monoxide intoxication had caused persistent disturbance of consciousness and quadriplegia. He had been tracheostomised and under nutrition by percutaneous endoscopic gastrostomy. On admission the presence of left pleural fluid with thickening of the pleura was shown on computed tomography. Thoracocentesis produced suppurative fluid with Actinomyces species nova identified by the 16S rRNA method. The patient was successfully treated with antibiotics and drainage of suppurative fluid.
[Show abstract][Hide abstract] ABSTRACT: We describe herein a newly defined pulmonary tumor presenting as an irregular shaped nodule in the peripheral lung, arising in a 62-year-old man. Histologically, the tumor showed papillary configuration, bronchioloalveolar spread, and a mucus lake, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. The tumor was diagnosed as ciliated muconodular papillary tumor of the peripheral lung.
Respiratory Medicine CME 01/2008; 1(2):176-178. DOI:10.1016/j.rmedc.2008.04.005
[Show abstract][Hide abstract] ABSTRACT: Isolates of M. tuberculosis were analyzed for their DNA fingerprints to facilitate understanding of ongoing transmission of tuberculosis in Sapporo (population 1.87 million), Japan, where the incidence rate of tuberculosis was 15.0 per 100,000 in 2004.
Out of all tuberculosis patients registered in the city from November 1998 to December 2003, isolates from culture-positive respiratory tuberculosis cases for whom written informed consent had been obtained, were analyzed by restriction fragment length polymorphism (RFLP). The study included 345 cases (249 men and 96 women) whose isolates were available for DNA patterns.
Using standard IS6110-RFLP typing, cases whose isolates shared identical fingerprints were considered to belong to the same cluster. Proportions of clustered cases were evaluated according to their clinical and socio-economical characteristics.
Out of 345 cases, 207 (60.0%) were classified into 59 clusters, and 15% of clustered cases having definite epidemiological links. Multiple logistic regression analysis in men showed that age and infectiousness were significantly related to clustering. The adjusted odds ratios (OR) [95% confidence intervals (CI)] were 0.17 [0.03-0.79] for 30-59 years, 0.15 [0.03-0.69] for 60 years or over and 2.35 [1.17-4.70] for those cases assigned as the highest level of transmission of tuberculosis from the infectiousness index of cases. For women the final model showed the adjusted OR [95% CI] were 0.52 [0.22-1.22] for those with previous history of tuberculosis and 0.33 [0.06-1.85] for diabetics. In male cases with a previous history of tuberculosis, most highly infectious cases were significantly associated with clustering (OR [95% CI], 4.53 [1.16-17.68]).
The results suggest that highly infectious male tuberculosis cases with endogenous reactivation have contributed to recent transmission of tuberculosis in the studied area.
[Show abstract][Hide abstract] ABSTRACT: To find a new method to predict the result of the egg based Ogawa medium using the Mycobacterium Growth Indicator Tube (MGIT) system and to evaluate the usefulness of a new discharge criterion that uses the new prediction method for smear positive pulmonary tuberculosis patients.
We compared mycobacterial growth of sputum specimens weekly between the Mycobacterium Growth Indicator Tube (MGIT) and the egg based Ogawa solid media, using a total of 3952 sputum specimens of patients with pulmonary tuberculosis (TB) who underwent chemotherapy in our hospital from September 2001 to March 2006 to find relationship between the results of the two culture methods and to utilize the findings to new discharge criteria of pulmonary TB patients. And we compared the duration of hospitalization between two patients' group: one group using the new discharge criterion, the other the old one.
We found that if a specimen shows negative culture on the MGIT system within the first two weeks, the same specimen shows negative or scant growth on the Ogawa media in the 8th week. Introducing this fact as a part of new criteria for hospital discharge of patients with pulmonary tuberculosis, the median duration of hospitalization in our hospital was shortened from 121 days to 71 days and no patient showed treatment failure.
We have used the result of sputum culture on Ogawa medium as a standard when we judge infectivity of patients with pulmonary tuberculosis in Japan, but it was one of the reasons why Japanese pulmonary tuberculosis patients stay long in TB hospital. Using our finding, we can predict the results of Ogawa system six weeks earlier, when a specimen shows negative culture on the MGIT system in the first 2 weeks. After we introduced this fact into new criteria for hospital discharge of patients with pulmonary tuberculosis, the median duration of hospitalization in our hospital was shortened and no patient shows treatment failure until now. We highly recommend the usefulness of the MGIT system (especially when a specimen shows negative growth in the first two weeks) as a reliable method of predicting infectivity of patients with pulmonary tuberculosis and propose that the new TB discharge criterion should be widely confirmed and used in other hospitals.
[Show abstract][Hide abstract] ABSTRACT: A 48-year-old man with dyspnea, cough, and fever was found to have a diffuse ground-glass pulmonary lesion without lymphadenopathy on chest X-ray. The lesion shifted to the peripheral lung zones 2 months later when transbronchial biopsy demonstrated noncaseating granulomas with Langhans type giant cells. After 6 more months, prominent bilateral hilar lymphadenopathy and highly elevated serum angiotensin-converting enzyme confirmed the diagnosis of pulmonary sarcoidosis. Such a course is quite rare in that it goes the opposite way of the conventional staging system.
Internal Medicine 02/2006; 45(13):819-22. DOI:10.2169/internalmedicine.46.1755 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We propose (-deltaG(rs)/deltat)/G(rs) obtained from Astograph as an index of dynamic property of the airway. G(rs) represents respiratory conductance. Fluid mechanics suggests that (- deltaG(aw)/deltat)/G(aw) is related to a coefficient of airway contraction or dilatation. G(aw) represents airway conductance. R(rs) (=1/G(rs)) is approximately equal to R(aw) (=1/G(aw)) + Constant. R(rs) and R(aw) represent respiratory and airway resistance, respectively. As R(rs) is thought to be closely correlated to R(aw), G(rs) should be correlated to G(aw). Thus, if G(rs) is used as a substitute for G(aw), (-deltaG(rs)/deltat)/G(rs) should also be related to a coefficient of airway contraction or dilatation. We found that asthmatics had significantly higher (-deltaG(rs)/deltat)/G(rs) than normal subjects. That is, the airway smooth muscles of the asthmatics are more contractive than those of normal subjects.
[Hokkaido igaku zasshi] The Hokkaido journal of medical science 02/2006; 81(1):9-13.
[Show abstract][Hide abstract] ABSTRACT: To assess the role of contrast-enhanced dynamic CT in the diagnosis of active tuberculoma.
Hospitals with an isolated ward for tuberculosis.
Fifty-five subjects with newly diagnosed active tuberculoma and 24 subjects with inactive tuberculoma were examined and evaluated retrospectively. Six subjects with active tuberculomas and seven subjects with inactive tuberculomas were confirmed by histologic and microbiologic evaluation of resected specimens, whereas the remainder of the subjects with tuberculoma were confirmed clinically. The subjects were receiving iopamidol, 370 mg/mL IV, at a rate of 3.0 mL/s on contrast-enhanced dynamic CT. The time-attenuation curve was obtained and adapted to a gamma function. The peak height (PH), maximum attenuation subtracted by the background attenuation, relative flow (RF), and mean regional flow were used for comparison. Measurements and results: In the surgically confirmed group, the PH and RF values of six subjects with active tuberculomas were significantly higher than those of the seven subjects with inactive tuberculoma (p < 0.05). Similarly, in the subjects with noninvasive diagnoses, the PH and RF values of 49 subjects with active tuberculoma were significantly higher than those of the subjects with inactive tuberculoma (mean +/- SD PH, 43.4 +/- 4.1 Hounsfield units [HU] vs 11.6 +/- 2.7 HU, p < 0.0001; RF, 0.012 +/- 0.001/s vs 0.006 +/- 0.001/s, p < 0.05). When the cutoff value was defined as mean +/- 2 SD, the sensitivity and specificity of the diagnosis for active tuberculoma were 77.1% and 96.4% in PH, and 68.5% and 88.8% in RF, respectively.
Contrast-enhanced dynamic CT is a potentially valuable tool for the diagnosis of active tuberculoma.
[Show abstract][Hide abstract] ABSTRACT: A 60-year-old woman was admitted for evaluation of an abnormal shadow in her chest X-ray. A chest roentgenogram revealed middle lobe atelectasis and a tomogram showed masses mainly in the right intermediate bronchus. In bronchoscopy, the bronchus was severely narrowed by irregularly surfaced masses. Microscopic examinations of transbronchial biopsy specimen showed the mucosal and submucosal tissue diffusedly infiltrated mainly by lymphocytes composed of small lymphocytes, centrocyte-like cells and monocytoid cells. The B-cell origin was suggested by a positive L-26 stain. Monoclonality of lymphocytes was proven by Southern blot analysis and in situ hybridization. The diagnosis was primary endobronchial lymphoma of mucosa-associated lymphoid tissue. The case was treated with chemotherapy protocol (CAMBO-VIP) and has been in complete remission for 20 months.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to examine the relationship between breathlessness and the ventilatory response to hypercapnia or hypoxia in patients with chronic obstructive pulmonary disease (COPD). Fifteen male patients (mean forced expiratory volume in one second (FEV1): 1.13 L) underwent tests to determine hyperoxic hypercapnic ventilatory response (HCVR) and isocapnic hypoxic ventilatory response (HVR) with simultaneous quantification of breathlessness by modified Borg scale. The ventilatory output was evaluated by the ratio of minute ventilation (V'E) divided by measured maximal voluntary ventilation (MVV). The magnitude of HCVR or HVR was assessed as the slope value of the V'E/MVV-end-tidal carbon dioxide pressure (PET,CO2) or arterial oxygen saturation (Sa,O2) regression line, respectively. The breathlessness during the tests was evaluated not only linearly in relation to V'E/MVV, but also at given levels of PET,CO2 or Sa,O2. The mean value of the breathlessness at two different levels of ventilation was greater during HVR than during HCVR, suggesting that hypoxia is dyspnogenic independently of ventilatory stimulation. The HCVR was inversely correlated with the breathlessness response to ventilation, while similar correlation was partly present for HVR. The HVR was positively correlated with the breathlessness at an Sa,O2 of 80%, whilst there was no such correlation between the HCVR and the breathlessness related to PET,CO2. Therefore, patients with a higher breathlessness related to increased ventilation had a lower HCVR and HVR, whilst those with a higher breathlessness with desaturation, which might include a direct influence of hypoxia, had a higher HVR. These findings suggest an interaction between ventilatory response and breathlessness during the test, which may partly include behavioural modulation of HCVR and HVR through the breathlessness in various ways, depending on the origin and nature of the sensation.
European Respiratory Journal 12/1996; 9(11):2340-5. DOI:10.1183/09031936.96.09112340 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined effects of selective M1 antagonists on hypercapnic and hypoxic ventilatory responses in 17 healthy human volunteers. Subjects were intravenously treated with placebo, pirenzepine (10 mg) and biperiden lactate (4 mg) on three separate days in a randomized double-blind design. Ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia were studied after the drug administration. There were no statistically significant differences in the mean ΔV̇e/ΔPetCO2 or ΔV̇e/ΔSaO2 among the three treatments. However, the ΔV̇e/ΔPetCO2 with placebo negatively correlated with the difference in ΔV̇e/ΔPetCO2 between the biperiden and placebo studies (r = −0.65, P < 0.01), but not with that between the pirenzepine and placebo studies. On the other hand, the V̇e/ΔSaO2 with placebo negatively correlated with the difference in V̇e/ΔSaO2 between the pirenzepine and placebo studies (r = −0.79, P < 0.001), but not with that between the biperiden and placebo studies. These data suggest the possible involvement of M1 cholinergic receptors in the central CO2 and peripheral O2 sensing mechanisms in humans, although the degree of its involvement is not consistent among subjects. These findings may explain the interindividual variation in the control of breathing in humans.
[Show abstract][Hide abstract] ABSTRACT: To examine the role of endogenous adenosine on the hypoxic ventilatory response (HVR) enhanced during exercise, we measured HVR at rest and during mild exercise (12.5 W) in nine healthy men in a supine position after pretreatment with aminophylline (5 mg/kg), an adenosine receptor blocker, or dipyridamole (0.6 mg/kg), an adenosine uptake blocker, by using a 3-day double-blind placebo-controlled design. Although HVR was enhanced during exercise on all occasions, HVR with aminophylline [0.42 +/- 0.07 (SE) l.min-1.%fall-1 of arterial O2 saturation] was significantly lower than that with placebo (0.64 +/- 0.13 l.min-1.%fall-1) or dipyridamole (0.64 +/- 0.08 l.min-1.%fall-1) during exercise (P < 0.05 for both) at similar end-tidal PCO2 on the 3 days but not at rest. We then examined the changes in plasma K+ concentration ([K+]) and catecholamines, the other possible endogenous potentiators of the carotid body activity. The exercise- and hypoxia-induced increases in plasma [K+] were significantly lower with aminophylline (0.23 +/- 0.09 meq/l) than with the placebo (0.51 +/- 0.10 meq/l) or dypyridamole (0.58 +/- 0.13 meq/l) (P < 0.05 for both). We therefore conclude that aminophylline attenuates the enhancement of HVR during mild exercise and that this might be due to its attenuating effect on exercise- and hypoxia-associated increases in plasma [K+] rather than due to its antagonizing effect on endogenous adenosine.
Journal of Applied Physiology 10/1994; 77(4):1763-8. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to examine the relationship between mechanical factors and the load compensation during hypercapnia in emphysema. In 36 clinically stable patients, we conducted pulmonary function tests and hypercapnic ventilatory response (HCVR) tests with and without inspiratory flow-resistive loading (IRL) (17 cm H2O/L/s). The mean value of HCVR significantly decreased with IRL, while that of the mouth occlusion pressure (P0.1) response increased. Regardless of IRL, the HCVR values were correlated with FEV1/FVC and airway resistance. The load compensation, evaluated by the ratio of the HCVR value and the P0.1 response before and after IRL, was inversely correlated with percent FRC (r = -0.38, r = -0.39; both p < 0.05). Breathing pattern analysis at the end-tidal pressure of carbon dioxide of 55 mm Hg elicited the decrease of (tidal volume/inspiratory time (VT/TI) and the increase of TI and TI/TTOT. Although the absolute changes of VT and f were inconsistent among subjects, each relative ratio before and after IRL was correlated again with percent FRC (r = -0.46, r = 0.44: both p < 0.01). Therefore, the position of the inspiratory muscles at the onset of inspiration may influence the load compensation during hypercapnia in emphysema.
[Show abstract][Hide abstract] ABSTRACT: To examine the role of endogenous adenosine in hypoxic ventilatory response, we measured, in nine normal young adults, ventilatory responses to isocapnic progressive hypoxia and subsequent sustained hypoxia [arterial O2 saturation (SaO2); 80%, 20 min] with and without pretreatment with dipyridamole in a double-blind crossover fashion. Dipyridamole, an adenosine uptake blocker, was expected to enhance the effect of endogenous adenosine. Pretreatment with dipyridamole (0.5 mg/kg) significantly augmented the slope of the ventilatory response to isocapnic progressive hypoxia from 0.35 +/- 0.13 (SE) to 0.70 +/- 0.25 l.min-1.%fall of SaO2(-1) (P < 0.01), although there were no significant changes in resting ventilation. On the other hand, minute ventilation, when expressed as a percentage of peak ventilation, declined to 68.4 +/- 4.3% with dipyridamole at the 9-11th min of sustained hypoxia, which was significantly lower than the 90.2 +/- 8.3% with a placebo (P < 0.05), and finally reached 56.1 +/- 7.2% with dipyridamole and 78.7 +/- 9.2% with the placebo (P < 0.1) at the 18-20th min of sustained hypoxia. In an attempt to more specifically examine the role of adenosine, aminophylline (5 mg/kg), an adenosine receptor antagonist, was injected before pretreatment with dipyridamole in four subjects. Aminophylline infusion abolished or at least attenuated the effect of dipyridamole in all four subjects. These data suggest that endogenous adenosine has a modulatory role in hypoxic ventilatory response in adult humans.
Journal of Applied Physiology 02/1994; 76(1):196-203. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify effects of aging on the load compensation response and the sensation of dyspnea, we examined 28 healthy male volunteers for ventilatory and P0.1 responses to hyperoxic progressive hypercapnia with and without inspiratory flow-resistive loading (17 cm H2O/L/s) while the intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Of the 28 subjects, 14 were 61 to 79 yr of age and were classified as the older group; the others, 19 to 48 yr of age, were classified as the control group. Neither delta VE/delta PETCO2 nor delta P0.1/delta PETCO2 was different between the two groups without loading. In the control group, the delta P0.1/delta PETCO2 increased with loading (p < 0.01) without a change in the delta VE/delta PETCO2. In the older group, the delta P0.1/delta PETCO2 did not change with loading so that the delta VE/delta PETCO2 decreased with loading (p < 0.01). In the 28 subjects as a whole, the percent change in delta P0.1/delta PETCO2 with loading was inversely correlated with age (r = -0.53, p < 0.01). At PETCO2 levels of 45, 50, and 55 mm Hg, irrespective of loading, the dyspnea intensity was greater in the older group than in the control group, whereas the P0.1 expressed as its ratio to the predicted maximal inspiratory mouth pressure was not different between the two groups. We conclude that aging attenuates the compensatory response to inspiratory flow-resistive loading and it increases the intensity of dyspnea for a given level of PETCO2.
The American review of respiratory disease 12/1993; 148(6 Pt 1):1586-91. DOI:10.1164/ajrccm/148.6_Pt_1.1586 · 10.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although theophylline, an adenosine receptor antagonist, is known to reduce cerebral blood flow, little clinical attention has been paid to this adverse effect. This study was designed to examine the effect of theophylline on brain tissue oxygenation for a wide range of arterial PO2 in healthy volunteers. Partial gas pressures and O2 saturation in an artery (SaO2) and the internal jugular vein (SjO2) were simultaneously measured while subjects (n = 6) were breathing room air and then exposed to two levels of isocapnic hypoxia (arterial PO2 = 60 and 45 Torr) before and after infusion of theophylline (6 mg/kg of aminophylline). For the same levels of arterial oxygenation, jugular vein PO2 markedly dropped, by 3-5 Torr, after theophylline infusion, as did SjO2, by as much as 6-10%, under the arterial PCO2, which was slightly lower by 1-2 Torr in the theophylline study. By use of the linear regression lines obtained from the relationship between SaO2 and SjO2 in each study, it was calculated that the SjO2 with theophylline, while SaO2 was 95, 90, and 80%, was comparable to that without theophylline when SaO2 was 81, 78, and 73%, respectively. On the basis of the assumption that partial gas pressures and SjO2 reflect brain tissue oxygenation, these data suggest that the effect of theophylline on brain tissue oxygenation should not be ignored in some clinical settings. The effects of chronic administration remain to be studied.
Journal of Applied Physiology 07/1993; 74(6):2724-8. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine possible genetic influence on the sensation of dyspnea and on load compensation, we conducted a twin study using healthy adult pairs (10 monozygotes, MZ, and 9 dizygotes, DZ). The ventilatory response to progressive hypercapnia (HCVR) was examined under three different conditions: hyperoxia (PETO2 > 150 mm Hg), hypoxia (PETO2 maintained at 50 to 55 mm Hg), and hyperoxia with an inspiratory flow-resistive load (17 mm H2O/L/s), with simultaneous assessment of the dyspnea sensation by visual analog scale (VAS). Although the VDZ/VMZ ratio (VMZ and VDZ are within-pair variances in MZ and DZ, respectively) for the slope value of the minute ventilation-PETCO2 regression line was not different from 1 in hyperoxia either with or without an inspiratory load, it was significantly larger than 1 in hypoxia (F = 5.17, p < 0.05), suggesting that a genetic influence on HCVR existed only in the presence of hypoxia. During 3% CO2 inhalation, the VDZ/VMZ ratio for the tidal volume (VT) was larger than 1 in hyperoxic HCVR with loading (F = 7.89, p < 0.01), and that for respiratory frequency (f) was larger than 1 only in hypoxic HCVR (F = 3.59, p < 0.05). At a PETCO2 of 55 mm Hg, the VT ratio was larger than 1 under all conditions (F = 5.91, p < 0.05; F = 6.99, p < 0.05; F = 3.75, p < 0.05; respectively), and the f ratio was significantly larger than 1 again only in hypoxic HCVR (F = 3.48, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The American review of respiratory disease 05/1993; 147(5):1192-8. DOI:10.1164/ajrccm/147.5.1192 · 10.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of conventional CT in the diagnosis of pulmonary emphysema (PE) was studied in 122 patients with miscellaneous diseases including 26 patients with PE. The density and the distribution of low attenuation area (LAA) were evaluated by six independent physicians. Analysis with kappa statistics showed a good inter-observer agreement in the detection of LAA. The grading of LAA correlated well with FEV1/FVC, DLCO/VA, and lung volumes, which indicated that PE could be detected by conventional CT by the evaluation of LAA. The agreement was poor, however, for the detection of low grade LAA and there were some false positives, and there was no specific pattern in the distribution of LAA in PE compared to other pulmonary diseases. We conclude that the evaluation of LAA by conventional CT is simple and effective in the screening of PE.