Assessment of pulmonary function in COPD patients using dynamic digital radiography: A novel approach utilizing lung signal intensity changes during forced breathing.

Objectives: To investigate the association of lung signal intensity changes during forced breathing using dynamic digital radiography (DDR) with pulmonary function and disease severity in patients with chronic obstructive pulmonary disease (COPD). Methods: This retrospective study included 46 healthy subjects and 33 COPD patients who underwent posteroanterior chest DDR examination. We collected raw signal intensity and gray-scale image data. The lung contour was extracted on the gray-scale images using our previously developed automated lung field tracking system and calculated the average of signal intensity values within the extracted lung contour on gray-scale images. Lung signal intensity changes were quantified as SImax/SImin, representing the maximum ratio of the average signal intensity in the inspiratory phase to that in the expiratory phase. We investigated the correlation between SImax/SImin and pulmonary function parameters, and differences in SImax/SImin by disease severity. Results: SImax/SImin showed the highest correlation with VC (rs = 0.54, P < 0.0001), followed by FEV1 (rs = 0.44, P < 0.0001), both of which are key indicators of COPD pathophysiology. In a multivariate linear regression analysis adjusted for confounding factors, SImax/SImin was significantly lower in the severe COPD group compared to the normal group (P = 0.0004) and mild COPD group (P=0.0022), suggesting its potential usefulness in assessing COPD severity. Conclusion: This study suggests that the signal intensity changes of lung fields during forced breathing using DDR reflect the pathophysiology of COPD and can be a useful index in assessing pulmonary function in COPD patients, potentially improving COPD diagnosis and management.

Hyperoxidized Peroxiredoxin 2 Is a Possible Biomarker for the Diagnosis of Obstructive Sleep Apnea.

Peroxiredoxin (Prx) 2 in red blood cells (RBCs) reacts with various reactive oxygen species and changes to hyperoxidized Prx2 (Prx2-SO2/3). Therefore, Prx2 may serve as an indicator of oxidative stress in vivo. This study aimed to analyze Prx2-SO2/3 levels in clinical samples to examine whether the oxidation state of Prx2 in human RBCs reflects the pathological condition of oxidative stress diseases. We first focused on obstructive sleep apnea (OSA), a hypoxic stress-induced disease of the respiratory system, and investigated the levels of Prx2-SO2/3 accumulated in the RBCs of OSA patients. In measurements on a small number of OSA patients and healthy subjects, levels of Prx2-SO2/3 accumulation in patients with OSA were clearly increased compared to those in healthy subjects. Hence, we proceeded to validate these findings with more samples collected from patients with OSA. The results revealed significantly higher levels of erythrocytic Prx2-SO2/3 in patients with OSA than in healthy subjects, as well as a positive correlation between the severity of OSA and Prx2-SO2/3 levels in the RBCs. Moreover, we performed a chromatographic study to show the structural changes of Prx2 due to hyperoxidation. Our findings demonstrated that the Prx2-SO2/3 molecules in RBCs from patients with OSA were considerably more hydrophilic than the reduced form of Prx2. These results implicate Prx2-SO2/3 as a promising candidate biomarker for OSA.

Projected lung area using dynamic X-ray (DXR) with a flat-panel detector system and automated tracking in patients with chronic obstructive pulmonary disease (COPD).

OBJECTIVES: To assess the association of projected lung area (PLA) measured by DXR with demographic data, pulmonary function, and COPD severity, and to generate PLA over time curves using automated tracking. METHODS: This retrospective study recruited healthy volunteers and COPD patients. Participants were classified into three groups: normal, COPD mild and COPD severe. PLA was calculated from the manually traced bilateral lung contours. PLA over time curves were produced using automated tracking, which was used to calculate slope and intercept by approximate line during forced expiration. The correlation of PLA, difference of PLA between end-inspiration and end-expiration (ΔPLA), slope, and intercept with demographic data and pulmonary function tests were investigated. The difference of PLA, ΔPLA, intercept, and slope among three groups were also evaluated. RESULTS: This study enrolled 45 healthy volunteers and 32 COPD patients. COPD severe group had larger PLA in both lungs at tidal/forced end-inspiration/expiration, smaller slope, and larger intercept than normal group (p < 0.001). PLA was correlated with % forced expiratory volume in one second (%FEV1) (rs from -0.42 to -0.31, p ≤ 0.01). ΔPLA in forced breathing showed moderate correlation with vital capacity (VC) (rs = 0.58, p < 0.001), while ΔPLA in tidal breathing showed moderate correlation with %FEV1 (rs = -0.52, p < 0.001) as well as mild correlation with tidal volume (rs = 0.24, p = 0.032). Intercept was slightly underestimated compared with manually contoured PLA (p < 0.001). CONCLUSION: COPD patients had larger PLA than healthy volunteers. PLA and ΔPLA in tidal breathing showed mild to moderate correlation with %FEV1.

Vector-field dynamic x-ray (VF-DXR) using optical flow method in patients with chronic obstructive pulmonary disease.

BACKGROUND: We assessed the difference in lung motion during inspiration/expiration between chronic obstructive pulmonary disease (COPD) patients and healthy volunteers using vector-field dynamic x-ray (VF-DXR) with optical flow method (OFM). METHODS: We enrolled 36 COPD patients and 47 healthy volunteers, classified according to pulmonary function into: normal, COPD mild, and COPD severe. Contrast gradient was obtained from sequential dynamic x-ray (DXR) and converted to motion vector using OFM. VF-DXR images were created by projection of the vertical component of lung motion vectors onto DXR images. The maximum magnitude of lung motion vectors in tidal inspiration/expiration, forced inspiration/expiration were selected and defined as lung motion velocity (LMV). Correlations between LMV with demographics and pulmonary function and differences in LMV between COPD patients and healthy volunteers were investigated. RESULTS: Negative correlations were confirmed between LMV and % forced expiratory volume in one second (%FEV1) in the tidal inspiration in the right lung (Spearman's rank correlation coefficient, rs = -0.47, p < 0.001) and the left lung (rs = -0.32, p = 0.033). A positive correlation between LMV and %FEV1 in the tidal expiration was observed only in the right lung (rs = 0.25, p = 0.024). LMVs among normal, COPD mild and COPD severe groups were different in the tidal respiration. COPD mild group showed a significantly larger magnitude of LMV compared with the normal group. CONCLUSIONS: In the tidal inspiration, the lung parenchyma moved faster in COPD patients compared with healthy volunteers. VF-DXR was feasible for the assessment of lung parenchyma using LMV.

Vector-Field dynamic X-ray (VF-DXR) using Optical Flow Method.

OBJECTIVES: To explore the feasibility of Vector-Field DXR (VF-DXR) using optical flow method (OFM). METHODS: Five healthy volunteers and five COPD patients were studied. DXR was performed in the standing position using a prototype X-ray system (Konica Minolta Inc., Tokyo, Japan). During the examination, participants took several tidal breaths and one forced breath. DXR image file was converted to the videos with different frames per second (fps): 15 fps, 7.5 fps, five fps, three fps, and 1.5 fps. Pixel-value gradient was calculated by the serial change of pixel value, which was subsequently converted mathematically to motion vector using OFM. Color-coding map and vector projection into horizontal and vertical components were also tested. RESULTS: Dynamic motion of lung and thorax was clearly visualized using VF-DXR with an optimal frame rate of 5 fps. Color-coding map and vector projection into horizontal and vertical components were also presented. VF-DXR technique was also applied in COPD patients. CONCLUSION: The feasibility of VF-DXR was demonstrated with small number of healthy subjects and COPD patients. ADVANCES IN KNOWLEDGE: A new Vector-Field Dynamic X-ray (VF-DXR) technique is feasible for dynamic visualization of lung, diaphragms, thoracic cage, and cardiac contour.

A case of allergic fungal rhinosinusitis caused by Schizophyllum commune identified in both patient's nasal sputum and veranda's soil samples.

This is a case report of allergic fungal rhinosinusitis caused by Schizophyllum commune (S. commune) identified in a patient's nasal mucus and environmental soil sample using (r)DNA sequencing. Although filamentous basidiomycetes, including S. commune, are known as environmental pathogens causing allergic respiratory diseases worldwide, many patients with infections caused by S. commune have not been correctly diagnosed. Repeated exposures to environmental floating fungi supposedly make an easy sensitization and colonization of fungi in the nasal passages, resulting in the onset of allergic fungal rhinosinusitis due to S. commune in our living environments. This report indicates the importance of reconsidering allergic respiratory diseases associated with our living environments.

Dynamic Chest X-Ray Using a Flat-Panel Detector System: Technique and Applications.

Dynamic X-ray (DXR) is a functional imaging technique that uses sequential images obtained by a flat-panel detector (FPD). This article aims to describe the mechanism of DXR and the analysis methods used as well as review the clinical evidence for its use. DXR analyzes dynamic changes on the basis of X-ray translucency and can be used for analysis of diaphragmatic kinetics, ventilation, and lung perfusion. It offers many advantages such as a high temporal resolution and flexibility in body positioning. Many clinical studies have reported the feasibility of DXR and its characteristic findings in pulmonary diseases. DXR may serve as an alternative to pulmonary function tests in patients requiring contact inhibition, including patients with suspected or confirmed coronavirus disease 2019 or other infectious diseases. Thus, DXR has a great potential to play an important role in the clinical setting. Further investigations are needed to utilize DXR more effectively and to establish it as a valuable diagnostic tool.

Projected lung areas using dynamic X-ray (DXR).

BACKGROUND: Dynamic X-ray (DXR) provides images of multiple phases of breath with less radiation exposure than CT. The exact images at end-inspiratory or end-expiratory phases can be chosen accurately. PURPOSE: To investigate the correlation of the projected lung area (PLA) by dynamic chest X-ray with pulmonary functions. MATERIAL AND METHODS: One hundred sixty-two healthy volunteers who received medical check-ups for health screening were included in this study. All subjects underwent DXR in both posteroanterior (PA) and lateral views and pulmonary function tests on the same day. All the volunteers took several tidal breaths before one forced breath as instructed. The outlines of lungs were contoured manually on the workstation with reference to the motion of diaphragm and the graph of pixel values. The PLAs were calculated automatically, and correlations with pulmonary functions and demographic data were analyzed statistically. RESULTS: The PLAs have correlation with physical characteristics, including height, weight and BMI, and pulmonary functions such as vital capacity (VC) and forced expiratory volume in one second (FEV1). VC and FEV1 revealed moderate correlation with the PLAs of PA view in forced inspiratory phase (VC: right, r = 0.65; left, r = 0.69. FEV1: right, r = 0.54; left, r = 0.59). Multivariate analysis showed that body mass index (BMI), sex and VC were considered independent correlation factors, respectively. CONCLUSION: PLA showed statistically significant correlation with pulmonary functions. Our results indicate DXR has a possibility to serve as an alternate method for pulmonary function tests in subjects requiring contact inhibition including patients with suspected or confirmed covid-19.

Time-resolved quantitative evaluation of diaphragmatic motion during forced breathing in a health screening cohort in a standing position: Dynamic chest phrenicography.

OBJECTIVE: To assess diaphragmatic motion during forced breathing in a health screening center cohort by time-resolved quantitative analysis using dynamic chest radiography and demonstrate the characteristics and associations with demographics and pulmonary function of participants. MATERIALS AND METHODS: This prospective study includes 174 volunteers (99 males; median 57, range 36-93 years old) that underwent dynamic chest radiography with a flat panel detector system during forced breathing in a standing position. We automatically tracked and recorded the positions of the top of the diaphragms and the excursions on images of each participant and calculated peak motion speeds based on the data. We investigated the associations with demographics and pulmonary function statistically. RESULTS: The average excursions of the diaphragms during forced breathing were 49.1 ± 17.0 mm (right; mean ± standard deviation) and 52.1 ± 15.9 mm (left). The peak motion speeds were 26.7 ± 10.0 mm/s (right) and 32.2 ± 12.4 mm/s (left) in the inspiratory phase and 22.1 ± 12.7 mm/s (right) and 24.3 ± 10.3 mm/s (left) in the expiratory phase. Excursions and peak motion speeds of the left diaphragm were significantly greater than the right. Higher body mass index (BMI) and vital capacity (VC) were associated with greater excursions and faster peak motion speeds of the diaphragms. CONCLUSIONS: Time-resolved quantitative analysis of the diaphragms with dynamic chest radiography demonstrated the characteristics of diaphragmatic motion during forced breathing in a health screening cohort. Higher BMI and VC were associated with excursions and peak motion speeds of the diaphragms.

Decreased and slower diaphragmatic motion during forced breathing in severe COPD patients: Time-resolved quantitative analysis using dynamic chest radiography with a flat panel detector system.

OBJECTIVE: To assess the diaphragmatic motion in chronic obstructive pulmonary disease (COPD) patients during forced breathing by time-resolved quantitative analysis using dynamic chest radiography and to demonstrate the characteristics and the difference from that in normal subjects. MATERIALS AND METHODS: Thirty-one COPD patients and a matched control of 31 normal subjects on age, sex, height, and weight, who underwent chest radiographs during forced breathing using dynamic chest radiography, were included in this study. COPD patients were classified based on the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (GOLD 1, n = 3; GOLD 2, n = 12; GOLD 3, n = 13; GOLD 4, n = 3). We measured excursions and peak motion speeds of the diaphragms for each participant. We compared the results among GOLD 1/2, GOLD 3/4 groups and normal subjects and investigated associations between the data, and participants' demographics, or pulmonary function. RESULTS: The excursions of bilateral diaphragms were significantly decreased in the GOLD 3/4 group relative to normal subjects (right, 39.8 ± 15.3 mm vs. 52.7 ± 15.1 mm, P = 0.030; left, 43.7 ± 14.0 mm vs. 56.9 ± 15.5 mm, P = 0.017; mean ± standard deviation) and the GOLD 1/2 group (right, 39.8 ± 15.3 mm vs. 54.4 ± 16.7 mm, P = 0.036; left, 43.7 ± 14.0 mm vs. 60.5 ± 13.9 mm, P = 0.008). The peak motion speeds of the left diaphragm in the inspiratory phase were slower in the GOLD 1/2 group than in normal subjects (24.5 ± 8.0 mm/s vs. 33.6 ± 14.0 mm/s, P = 0.038), and in the GOLD 3/4 group than in normal subjects (25.6 ± 6.8 mm/s vs. 33.6 ± 14.0 mm/s, P = 0.067). The excursions of the diaphragms showed correlation with VC, %VC, and FEV1, while the peak motion speeds showed no significant correlation with pulmonary function tests. CONCLUSIONS: Time-resolved quantitative analysis of diaphragms with dynamic chest radiography indicated differences in diaphragmatic motion between COPD groups and normal subjects during forced breathing. The excursions of the diaphragms during forced breathing were significantly lower in the GOLD 3/4 group than those in the GOLD 1/2 group and normal subjects.

Investigation of Obstructive Sleep Apnea Using Portable Monitors and Health Check Data in Japanese Drivers.

AIMS: The identification and appropriate management of commercial motor vehicle (CMV) drivers with unrecognized obstructive sleep apnea (OSA) is a major public health concern and priority; OSA among drivers has not been fully investigated in Japan, and a better understanding of this undiagnosed disease is warranted. Therefore, we evaluated the prevalence of OSA and the factors related to apnea-hypopnea index (AHI) in Japanese CMV drivers. METHODS: This retrospective study included 1309 Japanese CMV drivers aged 40-69 years. All the subjects received type Ⅳ portable sleep monitors (PMs) with Epworth Sleepiness Scale (ESS) and a periodic health check including anthropometrical and laboratory measurements, and a questionnaire of medical history, smoking status, and life style, following which variables related to AHI were analyzed. RESULTS: Of all the subjects, 23.9% had moderate to severe OSA (AHI ≥15). Age, body mass index (BMI), LogeHbA1c and diastolic blood pressure (DBP) showed significance with AHI in 1309 subjects. The following factors were found to have significant odds ratio (OR) for AHI of ≥15 in 1309 subjects: age, ESS, DBP, and LogeHbA1c. CONCLUSION: Notably, drivers with undiagnosed OSA exist. In these subjects, AHI was related to obesity, hypertension, and diabetes. For the early diagnosis and intervention of OSA, BMI, blood pressure, and HbA1c measurements may be helpful, particularly for drivers. Furthermore, when performing an objective assessment of the suspected OSA, evaluating these parameters during routine medical check-ups may be useful and feasible in the detection of drivers with latent OSA.

Difference in the craniocaudal gradient of the maximum pixel value change rate between chronic obstructive pulmonary disease patients and normal subjects using sub-mGy dynamic chest radiography with a flat panel detector system.

OBJECTIVES: To compare the craniocaudal gradients of the maximum pixel value change rate (MPCR) during tidal breathing between chronic obstructive pulmonary disease (COPD) patients and normal subjects using dynamic chest radiography. MATERIALS AND METHODS: This prospective study was approved by the institutional review board and all participants provided written informed consent. Forty-three COPD patients (mean age, 71.6±8.7 years) and 47 normal subjects (non-smoker healthy volunteers) (mean age, 54.8±9.8 years) underwent sequential chest radiographs during tidal breathing in a standing position using dynamic chest radiography with a flat panel detector system. We evaluated the craniocaudal gradient of MPCR. The results were analyzed using an unpaired t-test and the Tukey-Kramer method. RESULTS: The craniocaudal gradients of MPCR in COPD patients were significantly lower than those in normal subjects (right inspiratory phase, 75.5±48.1 vs. 108.9±42.0s-1cm-1, P<0.001; right expiratory phase, 66.4±40.6 vs. 89.8±31.6s-1cm-1, P=0.003; left inspiratory phase, 75.5±48.2 vs. 108.2±47.2s-1cm-1, P=0.002; left expiratory phase, 60.9±38.2 vs. 84.3±29.5s-1cm-1, P=0.002). No significant differences in height, weight, or BMI were observed between COPD and normal groups. In the sub-analysis, the gradients in severe COPD patients (global initiative for chronic obstructive lung disease [GOLD] 3 or 4, n=26) were significantly lower than those in mild COPD patients (GOLD 1 or 2, n=17) for both right and left inspiratory/expiratory phases (all P≤0.005). CONCLUSIONS: A decrease of the craniocaudal gradient of MPCR was observed in COPD patients. The craniocaudal gradient was lower in severe COPD patients than in mild COPD patients.

Difference in diaphragmatic motion during tidal breathing in a standing position between COPD patients and normal subjects: Time-resolved quantitative evaluation using dynamic chest radiography with flat panel detector system ("dynamic X-ray phrenicography").

OBJECTIVES: To quantitatively compare diaphragmatic motion during tidal breathing in a standing position between chronic obstructive pulmonary disease (COPD) patients and normal subjects using dynamic chest radiography. MATERIALS AND METHODS: Thirty-nine COPD patients (35 males; age, 71.3±8.4years) and 47 normal subjects (non-smoker healthy volunteers) (20 males; age, 54.8±9.8years) underwent sequential chest radiographs during tidal breathing using dynamic chest radiography with a flat panel detector system. We evaluated the excursions and peak motion speeds of the diaphragms. The results were analyzed using an unpaired t-test and a multiple linear regression model. RESULTS: The excursions of the diaphragms in COPD patients were significantly larger than those in normal subjects (right, 14.7±5.5mm vs. 10.2±3.7mm, respectively, P<0.001; left, 17.2±4.9mm vs. 14.9±4.2mm, respectively, P=0.022). Peak motion speeds in inspiratory phase were significantly faster in COPD patients compared to normal subjects (right, 16.3±5.0mm/s vs. 11.8±4.2mm/s, respectively, P<0.001; left, 18.9±4.9mm/s vs. 16.7±4.0mm/s, respectively, P=0.022). The multivariate analysis demonstrated that having COPD and higher body mass index were independently associated with increased excursions of the bilateral diaphragm (all P<0.05), after adjusting for other clinical variables. CONCLUSIONS: Time-resolved quantitative evaluation of the diaphragm using dynamic chest radiography demonstrated that the diaphragmatic motion during tidal breathing in a standing position is larger and faster in COPD patients than in normal subjects.

Time-Resolved Quantitative Analysis of the Diaphragms During Tidal Breathing in a Standing Position Using Dynamic Chest Radiography with a Flat Panel Detector System ("Dynamic X-Ray Phrenicography"): Initial Experience in 172 Volunteers.

RATIONALE AND OBJECTIVES: Diaphragmatic motion in a standing position during tidal breathing remains unclear. The purpose of this observational study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants' demographic characteristics. MATERIALS AND METHODS: One hundred seventy-two subjects (103 men; aged 56.3 ± 9.8 years) underwent sequential chest radiographs during tidal breathing using dynamic chest radiography with a flat panel detector system. We evaluated the excursions of and peak motion speeds of the diaphragms. Associations between the excursions and participants' demographics (gender, height, weight, body mass index [BMI], smoking history, tidal volume, vital capacity, and forced expiratory volume) were investigated. RESULTS: The average excursion of the left diaphragm (14.9 ± 4.6 mm, 95% CI 14.2-15.5 mm) was significantly larger than that of the right (11.0 ± 4.0 mm, 95% CI 10.4-11.6 mm) (P <0.001). The peak motion speed of the left diaphragm (inspiratory, 16.6 ± 4.2 mm/s; expiratory, 13.7 ± 4.2 mm/s) was significantly faster than that of the right (inspiratory, 12.4 ± 4.4 mm/s; expiratory, 9.4 ± 3.8 mm/s) (both P <0.001). Both simple and multiple regression models demonstrated that higher BMI and higher tidal volume were associated with increased excursions of the bilateral diaphragm (all P <0.05). CONCLUSIONS: The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher BMI and tidal volume are associated with increased excursions of the bilateral diaphragm.

Pneumothorax associated with nontuberculous mycobacteria: A retrospective study of 69 patients.

The incidence of nontuberculous mycobacterial pulmonary disease (NTMPD) is increasing worldwide. Secondary spontaneous pneumothorax occurs as a complication of underlying lung disease and is associated with higher morbidity, mortality, and recurrence than primary spontaneous pneumothorax. We here investigated the clinical features and long-term outcomes of pneumothorax associated with NTMPD.We conducted a retrospective study on consecutive adult patients with pneumothorax associated with NTMPD at Fukujuji Hospital and Keio University Hospital from January 1992 to December 2013. We reviewed the medical records of 69 such patients to obtain clinical characteristics, radiological findings, and long-term outcomes, including pneumothorax recurrence and mortality.The median age of the patients was 68 years; 34 patients were women. The median body mass index was 16.8 kg/m. Underlying pulmonary diseases mainly included chronic obstructive pulmonary disease and pulmonary tuberculosis. On computed tomography, nodules and bronchiectasis were observed in 46 (98%) and 45 (96%) patients, respectively. Consolidation, pleural thickening, interlobular septal thickening, and cavities were most common, and observed in 40 (85%), 40 (85%), 37 (79%), and 36 (77%) patients, respectively. Regarding pneumothorax treatment outcomes, complete and incomplete lung expansion were observed in 49 patients (71%) and 15 patients (22%), respectively. The survival rate after pneumothorax was 48% at 5 years. By the end of the follow-up, 33 patients had died, and the median survival was 4.4 years with a median follow-up period of 1.7 years. The rate of absence of recurrence after the first pneumothorax was 59% at 3 years. By the end of the follow-up, 18 patients had experienced pneumothorax recurrence. Furthermore, 12/18 patients (66%) with recurrent pneumothorax died during the study period. Twenty-three patients (70%) died because of NTMPD progression. Low body mass index (BMI) was a negative prognostic factor for pneumothorax associated with NTMPD in multivariate analysis (HR 0.79, 95% CI 0.64-0.96; P = 0.018)Patients with pneumothorax associated with NTMPD have advanced disease, a high rate of pneumothorax recurrence, and poor prognosis, regardless of the pneumothorax treatment used. Further improvements in early diagnosis of NTMPD and appropriate management in both NTMPD and NTMPD-associated pneumothorax are needed.

Sub-speciation of Mycobacterium tuberculosis complex from tuberculosis patients in Japan.

Mycobacterium tuberculosis is the major causative agent of tuberculosis in humans. It is well known that Mycobacterium bovis and other species in the M. tuberculosis complex (MTC) can cause respiratory diseases as zoonosis. We analyzed the MTC isolates collected from tuberculosis patients from Japan in 2002 using a multiplex PCR system that detected cfp32, RD9 and RD12. A total of 970 MTC isolates that were representative of the tuberculosis cases throughout Japan, were examined using this method. As a result, 966 (99.6%) M. tuberculosis, two Mycobacterium africanum and two Mycobacterium canettii were identified using a multiplex PCR system, while no M. bovis was detected. Two isolates that lacked RD9 were initially considered to be M. canettii, but further analysis of the hsp65 sequence revealed them to be M. tuberculosis. Also two M. africanum were identified as M. tuberculosis using the -215 narG nucleotide polymorphism. Though PCR-linked methods have been used for a rapid differentiation of MTC and NTM, from our cases we suggest careful interpretation of RD based identification.

Efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease caused by dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus, an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas and stabilize pulmonary function in patients with LAM. However, the optimal dose for the treatment of LAM remains unclear. METHODS: We conducted a retrospective, observational study of 15 patients with LAM who underwent sirolimus therapy for more than 6 months. The efficacy was evaluated by reviewing the patients' clinical courses, pulmonary function and chest radiologic findings before and after the initiation of sirolimus treatment. RESULTS: All patients had blood trough levels of sirolimus lower than 5ng/mL. Sirolimus treatment improved the annual rates of change in FVC and FEV1 in the 9 patients who were free from chylous effusion (FVC, -101.0 vs. +190.0mL/y, p=0.046 and FEV1, -115.4 vs. +127.8mL/y, p=0.015). The remaining 7 patients had chylous effusion at the start of sirolimus treatment; the chylothorax resolved completely within 1-5 months of treatment in 6 of these cases. These results resembled those of previous studies in which blood trough levels of sirolimus ranged from 5 to 15ng/mL. CONCLUSIONS: Low-dose sirolimus (trough level, 5ng/mL or less) performed as well as the higher doses used previously for improving pulmonary function and decreasing chylous effusion in patients with LAM.

[Clinical analysis of extensively-drug resistant tuberculosis (XDR-TB) in our hospital].

OBJECTIVE: We analyzed the clinical characteristics of extensively-drug resistant tuberculosis (XDR-TB). MATERIALS AND METHODS: Thirteen cases diagnosed with XDR-TB encountered in our hospital over the last ten years were enrolled in our study. RESULTS: The patients included 9 males and 4 females. The mean age was 49.1 years old in males and 42.0 years old in females. Eight patients were Japanese and 5 were foreigners (Chinese, 3; Korean, 1; Nepali, 1). Nine cases had a smoking history and 6 had underlying diseases, including 1 with bacterial pneumonia, 3 with diabetes mellitus, 1 with chronic renal failure, and 1 with collagen vascular disease receiving immunosuppressive treatment. All 13 cases had been diagnosed at other hospitals. The mean period from TB diagnosis to XDR-TB diagnosis was 56.8 months, and the mean period from TB diagnosis to referral to our hospital was 81.6 months. Among the 13 cases, 3 had no drug sensitivity, 1 was sensitive to only 1 drug, 2 were sensitive to 2 drugs, 6 were sensitive to 3 drugs, and 1 was sensitive to 4 drugs. Nine of the 13 cases had surgical treatment. Six cases, all of whom had surgical treatment, showed negative conversion in sputum examinations. Three patients died, including two who had surgical treatment. Among the 3 cases with no drug sensitivity, 1 was cured after surgical treatment. Another case had been working in the same hospital with two other MDR-TB cases. Two of the three had the same RFLP pattern. CONCLUSION: XDR-TB and MDR-TB are man-made diseases. We need to take measures not to create more XDR strains and induce more MDR-TB cases.

Clinical factors on cavitary and nodular bronchiectatic types in pulmonary Mycobacterium avium complex disease.

BACKGROUND AND OBJECTIVE: Pulmonary Mycobacterium avium complex (MAC) disease is the most common pulmonary non-tuberculous mycobacteriosis (NTM). The clinical and radiological findings were similar to those of pulmonary tuberculosis, both of which are characterized by upper lobe cavities. On the other hand, the presence of middle and lower field lesions with centrilobular nodules and bronchiectasis has been noted. We analyzed the clinical feature of these two radiologically different types and identified their prognostic factors. METHODS: The clinical, laboratory and radiological findings of 273 cases of MAC disease, newly diagnosed during the recent 7 years periods, were investigated. They were radiologically classified into cavitary (Cav) and nodular bronchiectasis (NB) types at the time of diagnosis. The findings of 44 fatal cases were compared with those of the newly diagnosed cases. RESULTS: A prominent increase in the number of cases was recently found only in females. Low body mass index (BMI) and moderately reduced serum albumin were found at the time of first hospital visit in both newly diagnosed and fatal cases. In the latter, peripheral blood lymphocyte count was slightly decreased, and tuberculin skin test was negative in 57.7% of the cases. Radiologically, Cav type was prevalent in males and NB type in females in the newly diagnosed cases, while in the fatal cases Cav type was frequently found in both males and females. The two radiological patterns did not change during the entire disease course. CONCLUSION: Cav type in females was one of the pathogenetic factors. Deterioration of cell-mediated immunity may underlie MAC disease.

[Case of multi-drug resistant pulmonary tuberculosis with bilateral cavitary lesions successfully treated by surgical treatment].

A case was 38 years old male. He was pointed out abnormal shadow on chest X-ray and complained respiratory infection symptoms. He had not past history of tuberculosis. He was diagnosed as multi-drug resistant tuberculosis (MDR-TB) in a certain hospital and was referred to our hospital to undergo treatment. His drug sensitivity test by Ogawa medium was resistant to all anti-tuberculosis drugs except for kanamycin (KM) and enviomycin (EVM). His chest X-ray revealed large cavities in the right upper field and infiltrations in the right lower field and small cavitary lesions in the left lower field. The right pneumonectomy was done because he took anti-tuberculosis drugs but his sputum examinations continued to be smear and culture positive without improvement of the lesions. After the surgical treatment (right pneumonectomy), he continued anti-tuberculosis drugs therapy and the chest X-ray improved including the collapse of left lower cavitary lesions. This case was a difficult case to treat because of bilateral cavitary lesions. However he was successfully treated by the surgical treatment.