Activities of Daily Living, Hypoxemia, and Lymphocytes Score for Predicting Mortality Risk in Patients With Pulmonary TB.

BACKGROUND: A clinically applicable mortality risk prediction system for pulmonary TB may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. The aim of this study was to construct a simple and objective disease severity score for patients with pulmonary TB. RESEARCH QUESTION: Does a clinical score consisting of simple objective factors predict the mortality risk of patients with pulmonary TB? STUDY DESIGN AND METHODS: The data set from our previous prospective study that recruited patients newly diagnosed with pulmonary TB was used for the development cohort. Patients for the validation cohort were prospectively recruited between March 2021 and September 2022. The primary end point was all-cause in-hospital mortality. Using Cox proportional hazards regression, a mortality risk prediction model was optimized in the development cohort. The disease severity score was developed by assigning integral points to each variate. RESULTS: The data from 252 patients in the development cohort and 165 patients in the validation cohort were analyzed, of whom 39 (15.5%) and 17 (10.3%), respectively, died in the hospital. The disease severity score (named the AHL score) included three clinical parameters: activities of daily living (semi-dependent, 1 point; totally dependent, 2 points); hypoxemia (1 point), and lymphocytes (< 720/µL, 1 point). This score showed good discrimination with a C statistic of 0.902 in the development cohort and 0.842 in the validation cohort. We stratified the score into three groups (scores of 0, 1-2, and 3-4), which clearly corresponded to low (0% and 1.3%), intermediate (13.5% and 8.9%), and high (55.8% and 39.3%) mortality risk in the development and validation cohorts. INTERPRETATION: The easy-to-calculate AHL disease severity score for patients with pulmonary TB was able to categorize patients into three mortality risk groups with great accuracy. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center; No. UMIN000012727 and No. UMIN000043849; URL: www.umin.ac.jp.

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.

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.

Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. METHODS: We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. RESULTS: In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. CONCLUSIONS: Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).

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.

Serum Procalcitonin Levels Predict Mortality Risk in Patients With Pulmonary Tuberculosis: A Single-Center Prospective Observational Study.

Globally, tuberculosis is the leading infectious cause of death; discovering biomarkers that predict a high mortality risk may improve treatment outcomes. We prospectively enrolled 252 pulmonary tuberculosis patients who were not coinfected with human immunodeficiency virus and initiated antituberculosis treatment, measured serum procalcitonin levels (PCT), and assessed mortality risk. PCT serum levels higher than 0.13 (day 0), 0.05 (day 7), 0.12 (day 14), or 0.06 (day 28) ng/mL predicted nonsurvivors with odds ratios of 7.9, 14.3, 20.0, and 7.3, respectively (P ≤ .005 for all), respectively. Therefore, serum PCT levels are a promising mortality risk indicator for patients with pulmonary tuberculosis. Main Point. For patients with pulmonary tuberculosis, a promising mortality risk indicator is the level of serum procalcitonin, which is weakly associated with sputum bacterial load and independent of radiographic findings.

Primary ciliary dyskinesia caused by a large homozygous deletion including exons 1-4 of DRC1 in Japanese patients with recurrent sinopulmonary infection.

BACKGROUND: Diffuse panbronchiolitis (DPB) is a sinopulmonary disease mainly affecting Asian populations. Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder impairing ciliary structure and function. These two disorders are not easily distinguished by clinical signs and symptoms. METHODS: In 105 Japanese patients with recurrent sinopulmonary infection, initially diagnosed with DPB, and 37 patients with recurrent airway infection diagnosed in adulthood, the deletion allele of DRC1 or CCDC164, recently recognized as a pathogenic PCD gene variant, was searched using a multiplexed PCR-based method, and the deletion breakpoints and other variants around the gene were determined by Sanger sequencing and targeted resequencing. RESULTS: A large homozygous deletion in DRC1 was identified in three of the 142 patients. Furthermore, heterozygous carriers of the deletion with the same breakpoint were found with the allele frequency of 0.002 in the healthy Japanese population, indicating that this loss-of-function variant may be acting as a common mutation causing PCD in Japanese. CONCLUSION: PCD caused by the DRC1 defect is not readily identified by either high-speed video-microscopy or ciliary ultrastructure analysis, posing significant difficulties in reaching a correct diagnosis without the aid of genetic tests. Careful investigation of the causes of sinopulmonary diseases is warranted in Asian populations.

Treatment of multidrug-resistant pulmonary tuberculosis with delamanid based on Japanese guideline recommendations.

BACKGROUND: In Japan, a new anti-tuberculous drug, delamanid, was recognized as the drug of choice to treat multi-drug resistant pulmonary tuberculosis in July 2014. METHODS: We treated 28 cases of multidrug-resistant tuberculosis (MDR-TB) and three cases of extensively drug-resistant tuberculosis (XDR-TB) with delamanid from July 2014 to June 2018 at our hospital. RESULTS: There were 21 men and 10 women, with the mean age of 48 and 37 years, respectively. We used an average of 4.4 sensitive anti-tuberculous drugs for the MDR-TB cases and 4.7 for the XDR-TB cases with delamanid. We used linezolid in 19 of 31 cases, although it has not been recognized as an anti-tuberculous drug in Japan. On electrocardiography, QTc prolongation of more than 450 ms was seen in two cases (6.4%), but they were asymptomatic, thus the treatment with delamanid could be continued. In 10 cases, surgical resection was performed. We completed the treatment in 20 cases and continued the treatment in seven cases; however, the treatment was discontinued in four cases because of side effects. In all cases, the sputum cultures were negative. CONCLUSIONS: Delamanid is a relatively safe drug with few side effects. However, some patients could not continue it because of difficulty of use in combination, therefore delamanid should be prescribed considering the side effects of all therapies in the regimen.

Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a relatively rare autosomal recessive or X-linked disorder affecting ciliary function. In the set of causative genes, however, predominant pathogenic variants remain unknown in Asia. METHOD: A diagnosis of PCD was made following a modern comprehensive testing including genetic analysis; targeted resequencing for screening variants, and Sanger sequencing for determination of the breakpoints, with an additional review of databases to calculate the deletion frequency. A multiplexed PCR-based detection method has also been developed. RESULTS: We ascertained a 50-year-old Japanese male who had been diagnosed with diffuse panbronchiolitis (DPB), but refractory to macrolide therapy. We reevaluated the case and identified a large homozygous deletion spanning exons 1 to 4 of the DRC1 and determined the breakpoints (NM_145038.4: c.1-3952_540 + 1331del27748-bp). In the PCD cohort at the University of North Carolina, we found a female PCD patient of Korean descent harboring the same homozygous deletion. From the Invitae testing cohort, we extracted four carriers of the same deletion among 965 Asian individuals, whereas no deletion was found in the 23,951 non-Asians. CONCLUSION: We speculate that the DRC1 deletion is a recurrent or perhaps founder mutation in Asians. The simple PCR method could be a useful screening tool.

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.

Longitudinal Evaluation of Humoral Immunity and Bacterial and Clinical Parameters Reveals That Antigen-Specific Antibodies Suppress Inflammatory Responses in Active Tuberculosis Patients.

A novel tuberculosis vaccine to replace BCG has long been desired. However, recent vaccine trials focused on cell-mediated immunity have failed to produce promising results. It is worth noting that most commercially available successful vaccines rely on humoral immunity. To establish a basic understanding of humoral immunity against tuberculosis, we analyzed and evaluated longitudinal levels and avidity of immunoglobulin to various tuberculosis antigens compared with bacterial and clinical parameters during treatment. We found that levels of IgG antibodies against HrpA and HBHA prior to treatment exhibited a positive correlation with bacterial burden. Analysis of changes in CRP during treatment revealed an association with high levels of specific IgG and IgA antibodies against mycobacterial antigens. Levels of CRP prior to treatment were negatively associated with IgG avidity to CFP-10 and MDP1 and IgA avidity to HrpA, while IgA avidity to MDP1 and Acr exhibited a negative correlation with CRP levels after 60 days of treatment. These results may provide insight for the development of a novel tuberculosis (TB) vaccine candidate to induce protective humoral immunity against tuberculosis.

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.

Pemetrexed-related interstitial lung disease reported from post marketing surveillance (malignant pleural mesothelioma/non-small cell lung cancer).

BACKGROUND: Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. METHODS: To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). RESULTS: ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. CONCLUSIONS: The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised.

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.