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Background/aims:Nutritional status is a factor affecting prognosis in patients with amyotrophic lateral sclerosis (ALS). Here, we aimed to clarify the factors associated with hypermetabolism and the prognosticators of ALS., Methods:Forty-two inpatients (22 men, 20 women) diagnosed with ALS according to the revised El-Escorial criteria were investigated. The following data were retrospectively analyzed: anthropometric measurements, blood biochemistry, disease severity, basal energy expenditure (BEE), resting energy expenditure (REE) measured by indirect calorimetry, spirometry, and bioelectrical impedance analysis. Single and multiple regression analysis was performed to examine factors affecting REE and metabolic changes (defined as the ratio of REE to fat-free mass [FFM]). The Kaplan-Meier method was used to examine factors associated with the occurrence of cumulative events (death or tracheostomy)., Results:Among the 42 inpatients, REE was significantly higher than BEE, indicating hypermetabolism in ALS. Multiple regression analysis revealed that REE/FFM is strongly associated with the skeletal muscle index (-3.746 to -1.532, p < 0.0001) and percent forced vital capacity (%FVC) (-0.172 to -0.021, p = 0.013). Moreover, both the skeletal muscle index and %FVC were significant prognosticators associated with the occurrence of cumulative events., Conclusions:Energy metabolism was elevated in ALS, and respiratory status and muscle mass were associated with the hypermetabolism and poor prognosis. Adequate nutritional support may improve outcomes in ALS by preventing deterioration of respiratory status and reduction in muscle mass.

Background : Although platinum-combination chemotherapy is widely used to treat advanced non-small cell lung cancer (NSCLC), not all elderly patients benefit from this regimen. In this retrospective study, we aimed to evaluate whether the Glasgow Prognostic Score (GPS), an indicator of systemic inflammation and malnutrition, could predict the tolerability and efficacy of platinum-combination chemotherapy among elderly patients with NSCLC. Methods : The eligibility criteria included patients aged ≥ 70 years with NSCLC treated with first-line platinum-combination chemotherapy at Shimane University Hospital between January 2015 and December 2018. Results : Thirty-two patients with NSCLC (median age, 74 years) were included. The GPS scores were 0-1 for 19 patients and 2 for 13 patients. Four chemotherapy cycles were completed by 57.9% and 30.8% of patients in the GPS 0-1 and GPS 2 groups, respectively. The GPS 0-1 group experienced better outcomes than the GPS 2 group (response rate : 26% vs. 15%, P = 0.67 ; median progression-free survival : 4.1 vs. 2.1 months, P = 0.0026 ; median overall survival : 22.8 vs. 9.6 months, P = 0.0092). Conclusions : Platinum-combination chemotherapy demonstrated promising efficacy among elderly NSCLC patients with a GPS 0-1. Therefore, GPS may be crucial in determining whether treatments recommended for younger patients are suitable for older patients with NSCLC. J. Med. Invest. 68 : 260-264, August, 2021.

Purpose The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology. Patients and methods FOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes. Results √Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value. Conclusion The FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments.

Background Some randomized controlled trials have evaluated the effects of low-dose computed tomography (CT) screening on lung cancer mortality in heavy smokers. Based on the results of those trials, our CT screening program recommended screening for people aged ≥40 years with a history of smoking. This retrospective study aimed to verify the validity of our CT screening program and elucidate the current state of CT screening program. Methods We retrospectively examined lung cancer detection in 25,189 participants who underwent chest CT screening by a mobile low-dose CT screening unit in the 10-year period from April 2009 to March 2019. Participants were recruited at Japan Agricultural Cooperatives (JA) Shimane Kouseiren. Participants requested CT screening for lung cancer. CT images were read by two pulmonologists. Results Lung cancer was identified in 82 of the 25,189 participants over 10 years, an overall lung cancer detection rate (percentage of lung cancers detected among all participants) of 0.33%. Lung cancer among never smokers accounted for 54.9% of the detected cases. The lung cancer detection rate was similar for smokers versus never smokers. The stage IA detection rate (percentage of stage IA lung cancers among all lung cancers detected) was 62%, while the stage Ⅳ detection rate was 10%. Conclusions Chest CT detected lung cancer in never smokers as well as current or former smokers. Our CT screening program was not effective for never smokers; thus, further study of the effectiveness of CT screening in never smokers is needed.

The constraint values of dose-volume histogram (DVH) parameters for radiation pneumonitis (RP) prediction have not been uniform in previous studies. We compared the differences between conventional DVH parameters and DVH parameters with high attenuation volume (HAV) in CT imaging in both esophageal cancer and lung cancer patients to determine the most suitable DVH parameters in predicting RP onset. Seventy-seven and 72 patients who underwent radiation therapy for lung cancer and esophageal cancer, respectively, were retrospectively assessed. RP was valued according to the Common Terminology Criteria for Adverse Events. We quantified HAV with quantitative computed tomography analysis. We compared conventional DVH parameters and DVH parameters with HAV in both groups of patients. Then, the thresholds of DVH parameters that predicted symptomatic RP and the differences in threshold of DVH parameters between lung cancer and esophageal cancer patient groups were compared. The predictive performance of DVH parameters for symptomatic RP was compared using the area under the receiver operating characteristic curve. Mean lung dose, HAV30% (the proportion of the lung with HAV receiving ≥30 Gy), and HAV20% were the top three parameters in lung cancer, while HAV10%, HAV5%, and V10 (the percentage of lung volume receiving 10 Gy or more) were the top three in esophageal cancer. By comparing the differences in the threshold for parameters predicting RP between the two cancers, we saw that HAV30% retained the same value in both cancers. DVH parameters with HAV showed narrow differences in the threshold between the two cancer patient groups compared to conventional DVH parameters. DVH parameters with HAV may have higher commonality than conventional DVH parameters in both patient groups tested.

BackgroundHoneycombing on high-resolution computed tomography (HRCT) images is a key finding in idiopathic pulmonary fibrosis (IPF). In IPF, honeycombing area determined by quantitative CT analysis is correlated with pulmonary function test findings. We hypothesized that quantitative CT-derived honeycombing area (HA) might predict mortality in patients with IPF.Materials and methodsChest HRCT images of 52 IPF patients with definite usual interstitial pneumonia (UIP) pattern were retrospectively evaluated. Mortality data up to July 31, 2016, were recorded. Using a computer-aided system, HA and percentage of HA (%HA) were measured quantitatively. Predictors of 3-year mortality were evaluated using logistic regression models.ResultsThe median %HA, %predicted forced vital capacity (FVC) and composite physiologic index (CPI) were 3.8%, 83.6%, and 33.6, respectively. According to GAP (gender, age, and physiology) stage, 20, 14, and 5 patients were classified under stages I-II-III, respectively. Percentage of HA was significantly correlated with %FVC, CPI, and GAP stage (all, p < 0.001). In univariate analysis, %HA, %FVC, and CPI were statistically significant predictors of mortality. In multivariate analysis using the stepwise regression method, only %HA (odds ratio [OR], 1.27; p = 0.011) was a significant independent predictors of mortality. Patients with %HA ≥ 4.8% had significantly lower survival rates than those with lesser %HA (median survival time, 1.3 vs 5.0 years; log-rank test; p < 0.001).ConclusionQuantitative CT-derived HA might be an important and independent predictor of mortality in IPF patients with definite UIP pattern.

Objectives The 2011 official statement of idiopathic pulmonary fibrosis (IPF) mentions that the extent of honeycombing and the worsening of fibrosis on high-resolution computed tomography (HRCT) in IPF are associated with the increased risk of mortality. However, there are few reports about the quantitative computed tomography (CT) analysis of honeycombing area. In this study, we first proposed a computer-aided method for quantitative CT analysis of honeycombing area in patients with IPF. We then evaluated the correlations between honeycombing area measured by the proposed method with that estimated by radiologists or with parameters of PFTs. Materials and methods Chest HRCTs and pulmonary function tests (PFTs) of 36 IPF patients, who were diagnosed using HRCT alone, were retrospectively evaluated. Two thoracic radiologists independently estimated the honeycombing area as Identified Area (IA) and the percentage of honeycombing area to total lung area as Percent Area (PA) on 3 axial CT slices for each patient. We also developed a computer-aided method to measure the honeycombing area on CT images of those patients. The total honeycombing area as CT honeycombing area (HA) and the percentage of honeycombing area to total lung area as CT %honeycombing area (%HA) were derived from the computer-aided method for each patient. Results HA derived from three CT slices was significantly correlated with IA ( ρ =0.65 for Radiologist 1 and ρ =0.68 for Radiologist 2). %HA derived from three CT slices was also significantly correlated with PA ( ρ =0.68 for Radiologist 1 and ρ =0.70 for Radiologist 2). HA and %HA derived from all CT slices were significantly correlated with FVC (%pred.), DL CO (%pred.), and the composite physiologic index (CPI) (HA: ρ =−0.43, ρ =−0.56, ρ =0.63 and %HA: ρ =−0.60, ρ =−0.49, ρ =0.69, respectively). Conclusions The honeycombing area measured by the proposed computer-aided method was correlated with that estimated by expert radiologists and with parameters of PFTs. This quantitative CT analysis of honeycombing area may be useful and reliable in patients with IPF.

Background and objective The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts. Methods Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of −950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1/FVC and FEV1% predicted. Results Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) or FEV1% predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2−3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts. Conclusions %LAV predicts both FEV1/FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

OBJECTIVE Early detection of chronic obstructive pulmonary disease (COPD) is critical for preventing progression; however, the disease is rarely detected in the early stages. One reason for this is that COPD is not generally recognized and diagnosed by general practitioners (GPs). The objective of this study was to observe changes in the knowledge and behavior of GPs regarding the diagnosis and treatment of COPD over a five-year period. METHODS The surveys were performed using identical and anonymous questionnaires in 2005, 2006 and 2010. During this period, various educational campaigns were conducted. MATERIALS All members of the Shiga Medical Association working as GPs in Shiga Prefecture. RESULTS The number of questionnaires collected was 216 of 711, 269 of 731 and 326 of 856, respectively. Throughout the study period, the number of doctors who prescribed inhaled long-acting muscarinic antagonists (LAMAs) significantly increased (p

Introduction: Eosinophilic airway inflammation is now recognized as one of the important pathophysiology of chronic obstructive pulmonary disease (COPD). Objectives: To investigate the usability of fractional exhaled nitric oxide (FeNO) as a maker of eosinophilic inflammation compared with other biomarkers like blood eosinophil counts and serum IgE level in stable COPD patients. Patients and methods: A total of 146 stable COPD patients were enrolled from the outpatient clinic of respiratory medicine in our hospital from May 2011 to June 2016. The patients underwent spirometry and chest CT. FeNO was measured before spirometry. Peripheral blood eosinophil counts and serum IgE level were also measured. Using chest CT data, emphysematous lesions and the airway wall thickness were assessed by the percentage of low attenuation voxels (LAV%) and by the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. Results: The participants were 10 females and 136 males with a mean age of 71.8 ± 7.3 (mean ± SD) years old. FEV1 %predicted was 68.5 ± 21.2% and FeNO was 29 ± 20 ppb. Laboratory findings showed that blood eosinophils were 237.0 ± 181.1/μL, and median serum IgE was 121.4 IU/ml (IQR, 27.9 - 439.3 IU/ml). FeNO was positively correlated with serum IgE (p=0.003), but not correlated with blood eosinophils (p=0.064). Serum IgE and blood eosinophils were positively correlated with each other (p=0.03). FeNO was not correlated with CT measured markers such as LAV% and √Aaw at Pi10. Conclusions: FeNO can be an easy, noninvasive and useful marker of eosinophilic airway inflammation in stable COPD patients.

BACKGROUND: Many patients with idiopathic pulmonary fibrosis (IPF) have smoking history and emphysematous lesions. However, there are no reports using quantitative computed tomography (CT) analysis of both emphysema and fibrosis in IPF patients. We have recently reported the method to quantify honeycombing area (HA) using CT. We hypothesized that the extent of fibrosis and emphysema might predict the survival in IPF. In this study, we measured both HA and emphysematous area in IPF patients with smoking history. METHODS: Chest CTs of 61 IPF patients were retrospectively evaluated. We first measured HA and then calculated the emphysematous area as subtracted Low Attenuation Area (sLAA). The percentage of HA and sLAA to total lung area were also calculated (%HA and %sLAA, respectively). RESULTS: The mean %HA and %sLAA were 4.5% and 21.5%, respectively. The optimal cut-off values for survival of %HA and %sLAA were set at 5% and 10% by receiver operating characteristic curve. Patient with %HA more than 5% had significantly lower survival rate (Median survival time (MST): 1.8 vs 5.9 years; log-rank: p=0.0037). Patient with %sLAA more than 10% had significantly higher survival rate (MST: 4.3 vs 1.8 years; log-rank: p=0.0001). Combined %HA with %sLAA (%HA≥5% and %sLAA CONCLUSION: %HA and %sLAA may predict the survival of IPF patients with smoking history.

Background: Forced oscillation technique (FOT) has been applied to chronic obstructive pulmonary disease (COPD) as a useful method to assess respiratory resistance and reactance. We hypothesized that the FOT data could reflect the pathophysiological change and the progression of COPD. Methods: One hundred eighteen COPD patients and 28 non-COPD smokers were enrolled. Chest CT scan, pulmonary function tests and FOT were performed annually. For the quantification of emphysematous lesions and airway lesions, the percentage of low attenuation volume (LAV%) and the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) were measured by chest CT scan. Results: The COPD patients were divided into four phenotypes based on R5 and X5 of the non-COPD smokers: the normal like group (NL), the resistance dominant group (RD), the reactance dominant group (XD), and the mixed group (MIX).Relationship between severity of airflow limitation and the phenotypes revealed that the ratio of NL tended to be decreased and the ratio of MIX tended to be increased when the airflow limitation worsened. RD were limited in mild and moderate airflow limitation, while XD can be observed from mild to very sever groups. These tendency was also observed in a longitudinal analysis (after 1 year and 2 years). Among NL and RD at baseline, 10 patients whose X5 worsened after 1 year follow-up were significantly older and had lower FEV1 at baseline. On the other hand, among MIX at baseline, the 9 patients whose R5 and/or X5 improved had significantly lower √Aaw at Pi10 at baseline. Conclusion: The FOT-based phenotypes might give us a new aspect for the assessment of COPD progression.

Williams-Campbell syndrome is a rare disease, characterized by a congenital deficiency of cartilage in the fourth to sixth order bronchi, leading to chronic respiratory failure with recurrent pulmonary infections. An effective and practical treatment has not yet been established. A 31-year-old man who was diagnosed as Williams-Campbell syndrome by inspiratory and expiratory computed tomography findings developed recurrent pulmonary infections and showed progressive deterioration of dyspnea. Domiciliary NPPV was administered, followed by a dramatic improvement of respiratory failure and a decrease in the episodes of pulmonary infections. NPPV may have an advantage in adults with Williams-Campbell syndrome who have severe respiratory failure and recurrent pulmonary infections.

Background and objective: COPD is one of the leading causes of morbidity and mortality worldwide, and its prevalence continues to increase. Although spirometry is indispensable for the diagnosis of COPD, other simple and reliable tools are necessary for screening of COPD because spirometry is not widely available. This study investigated the usefulness of a combination of an electronic FEV1/FEV6 meter (PiKo-6) with a COPD questionnaire as a screening method in patients with cardiovascular diseases. Methods: The PiKo-6 and the COPD questionnaire of the International Primary Care Airways Group were used to screen patients attending a cardiovascular outpatient clinic. Patients with FEV1/FEV6

To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension.Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on.University hospital.Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years.RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP17 mm Hg, n = 24) [p0.001]; 70.4% in the preserved-Dlco group (percentage of predicted40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted40%, n = 25) [p0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2.Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.

A 17-year-old teen was hospitalized with bilateral pneumothorax. After the bilateral lungs were expanded using catheter tubes, he fully recovered and he was discharged from our hospital. He had a history of colon perforation. Ehlers-Danlos syndrome (EDS) was suspected due to the combination of colon perforation and pneumothorax, and EDS type IV was confirmed after a genetic study identified a c.1511g>a mutation in the COL3A1 gene. This is the first report of bilateral pneumothorax caused by EDS type IV. Clinicians should consider EDS type IV in the differential diagnosis for bilateral pneumothorax in conjunction with distinct previous histories and radiological findings.

Quantitative computed tomography (CT) has been used to phenotype patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is defined as the presence of both airway wall thickening and emphysema on quantitative CT. Little is known about patients with COPD with the mixed phenotype.To propose a method of phenotyping COPD based on quantitative CT and to compare clinically relevant outcomes between patients with COPD with the mixed phenotype and those with other CT-based phenotypes.Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete medical interview, pulmonary function testing, and whole-lung CT on the same day. The percentage of low-attenuation volume at the threshold of -950 Hounsfield units (%LAV) and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were classified into four distinct phenotypes based on the upper limits of normal for %LAV and Pi10, which were derived from the data of smokers without COPD by using quantile regression.Of 240 patients with COPD, 52 (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed phenotype. Patients with COPD with the mixed phenotype were associated with more severe dyspnea than those with each of the remaining CT-based phenotypes (P 0.01 for all comparisons). The number of hospitalizations for COPD exacerbations during the preceding year was 2.0 to 3.6 times higher in patients with the mixed phenotype than in those with each of the remaining CT-based phenotypes (P 0.05 for all comparisons). Findings persisted after adjustment for age, pack-years of smoking, smoking status, body mass index, and FEV1.Patients with COPD with the mixed phenotype are associated with more severe dyspnea and more frequent hospitalizations than those with each of the remaining CT-based phenotypes. Thus, patients with COPD with the mixed phenotype may need more attention and interventions.

Chronic obstructive pulmonary disease is characterized by destruction of the lung parenchyma and/or small airway narrowing. To determine whether the dimensions of relatively large airways assessed using computed tomography (CT) reflect small airway dimensions measured histologically, we assessed these variables in nonobstructed or mild to moderately obstructed patients having lobar resection for a peripheral tumor. For both CT and histology, the square root of the airway wall area (Aaw) was plotted versus lumen perimeter to estimate wall thickness. The wall area percentage was calculated as wall area/lumen area + wall area x 100. Although CT overestimated Aaw, the slopes of the relationships between the square root of Aaw and internal perimeter (Pi) measured with both techniques were related (CT slope = 0.2059 histology slope + 0.1701, R2 = 0.32, p0.01). The mean wall area percentage measured by CT for airways with a Pi of greater than 0.75 cm predicted the mean dimensions of the small airways with an internal diameter of 1.27 mm (R2 = 0.57, p0.01). We conclude that CT measurements of airways with a Pi of 0.75 cm or more could be used to estimate the dimensions of the small conducting airways, which are the site of airway obstruction in chronic obstructive pulmonary disease.

Wereport the case of a 58-year-old woman who was considered to have died of cyclophosphamide (CPA)-induced late-onset lung disease. She underwent a right-sided mastectomy due to breast cancer at the age of 50 followed by daily administration of 50 mg CPA and 20 mg tamoxifen for 2 years. A refractory cough and dyspnea began at the age of 56. Chest radiographs revealed diffuse infiltrates and pleural thickening. Her vital capacity was markedly reduced. Corticosteroid therapy was ineffective. The disease rapidly progressed with occasional episodes of pneumothoraces to her death. Postmortem examination revealed pulmonary fibrosis with marked elastosis.(Internal Medicine 42: 82-87, 2003)

Background: The development of well-matured fibrosis in usual interstitial pneumonia (UIP) is strongly associated with an unfavorable outcome of patients with idiopathic pulmonary fibrosis (IPF). However, differences in the rates of development are likely to result in variable clinical courses in IPF patients. Objective: We tried to evaluate the progression of honeycombing and ground-glass opacity on CT using a scoring system, and to examine those serial changes in the clinical course of disease. Methods: A hospital-based, retrospective cohort study. Twenty-three patients with IPF diagnosed as UIP by surgical lung biopsy were analyzed during the initial examination by scoring the presence of honeycombing (HC: range, 0–24) and ground-glass opacity (GG: range, 0–24) on CT scan. We also compared the serial changes observed in the CT scores (interval: 2–42 months, 2–6 examinations). Results: (1) The serial change in the HC score in treated patients (n = 10) was similar to that in untreated patients (n = 16); (2) the HC score at the time of the initial examination and the rate of HC progression were both higher in the non-surviving patients (HC 12.3 ± 3.7, mean ± SD; ΔHC 4.2 ± 1.3 per year) than in the surviving patients (HC 5.8 ± 2.7; ΔHC 1.2 ± 0.7 per year) (p < 0.05); (3) the GG score did not correlate with the HC score at any of the examinations; (4) the HC score was higher in the lower lung field than in the upper and middle lung fields. Conclusions: Scoring of the honeycombing and its serial changes using the high-resolution computed tomography scoring method was useful for predicting the prognosis in patients with IPF/UIP. Corticosteroid treatment did not prevent the progression of HC.

The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts.Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of -950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1 /FVC and FEV1 % predicted.Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) or FEV1 % predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2-3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts.%LAV predicts both FEV1 /FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

Background: Bronchoalveolar lavage fluid (BALF) lymphocytosis was found in patients with usual interstitial pneumonia (UIP) associated with collagen vascular diseases (CVD) other than diffuse systemic sclerosis (SSc), but it was not found in patients with idiopathic pulmonary fibrosis (IPF), a disease histologically diagnosed as UIP. This difference could be partly due to variations of UIP spectrums between IPF and interstitial pneumonia associated with CVD. Methods: We scored histopathological findings of lung specimens obtained from 31 cases (16 IPF, 9 CVD other than SSc and 6 SSc) using a semiquantitative scoring method. All cases were diagnosed as UIP by surgical lung biopsy. None of the patients were current smokers. Results: Compared with IPF and SSc cases, CVD patients without SSc presented decreased scores of fibrosis (p < 0.01) and alveolar space cellularity (severity, p < 0.05). Lymphocytes were mainly localized in the alveolar walls and the majority of cells in the alveolar spaces were macrophages. On the other hand, other scores such as cellularity and alveolar wall cell infiltrate did not vary among these three groups. Conclusion: Fewer macrophages in the alveolar spaces and a decrease in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with UIP/CVD non-SSc than in patients with IPF/UIP and UIP-SSc.

BackgroundIt is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers.MethodsPulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe.ResultsUsing a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R(2) = 0.78, PConclusionIn male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs.

A 77-year-old woman with Sjogren's syndrome has been followed for mild interstitial pneumonia. A 2-cm pulmonary nodule was incidentally found in the left lower lobe, and positron emission tomography-computed tomography showed 18 F-fluorodeoxyglucose uptake with a maximum standardized uptake value of 8.78 in this nodule. Although this suggested a malignant disease, transbronchial biopsy of the nodule revealed that it was cholesterol granuloma. It is known that some benign inflammatory diseases show an increased uptake of 18 F-fluorodeoxyglucose, particularly granulomatous lesions like tuberculosis. To our knowledge, this is the first report of 18 F-fluorodeoxyglucose-positron emission tomography findings for cholesterol granuloma. We speculate that increased 18 F-fluorodeoxyglucose uptake with cholesterol granuloma occurs through cellular infiltration and macrophage proliferation, resulting in the activation of glycolysis-like tuberculosis.

We report a case of a 60-year-old woman who developed a tracheal fistula 20 months after mediastinal radiation while being treated with bevacizumab. She presented with a large right-sided mediastinal mass given a diagnosis of stage IIIB adenocarcinoma. She was treated with definitive thoracic radiation (figure 1) and a concurrent chemotherapy, including both cisplatin and docetaxel. Eleven months after chemoradiotherapy …

A 69-year-old Japanese woman with multiple brain metastases secondary to non-small-cell lung cancer was treated with radiosurgery, and subsequently started oral gefitinib. Three years later, she presented with erythematous erosive alopecia with pustules on the scalp. A biopsy specimen showed a dense perifollicular infiltration composed of lymphocytes, neutrophils and abundant plasma cells. Methicillin-resistant Staphylococcus aureus was cultured from the lesions; however, treatment with antibiotics was not effective. We diagnosed an eruption resembling erosive pustular dermatosis of the scalp. Although oral steroids did not improve the lesions, the pustules and erythema of the scalp rapidly improved within a few weeks after discontinuation of gefitinib. There have been only 11 case reports of alopecia associated with epidermal growth factor receptor (EGFR) inhibitors including our case. It is noteworthy that all cases were female, and most cases involved the parietal scalp. Moreover, the reduction or discontinuation of the EGFR inhibitors was needed in all cases with erythematous alopecia, which remained as scarring alopecia.

COPD is one of the leading causes of morbidity and mortality worldwide, and its prevalence continues to increase. Although spirometry is indispensable for the diagnosis of COPD, other simple and reliable tools are necessary for screening of COPD because spirometry is not widely available. This study investigated the usefulness of a combination of an electronic FEV₁/FEV₆ meter (PiKo-6) with a COPD questionnaire as a screening method in patients with cardiovascular diseases.The PiKo-6 and the COPD questionnaire of the International Primary Care Airways Group were used to screen patients attending a cardiovascular outpatient clinic. Patients with FEV₁/FEV₆70% were defined as having airflow limitation. Patients diagnosed with airflow limitation underwent spirometry. Using data from the PiKo-6 and the COPD questionnaire, patients were assigned to a COPD group or a non-COPD group. The relationship between PiKo-6 measurements and spirometry was also evaluated.Among 753 patients, 82 (10.9%) showed airflow limitation when assessed with the PiKo-6. Of these patients, 79 (10.5%) were assigned to the COPD group. FEV₁, FEV₆ and FEV₁/FEV₆, as measured with the PiKo-6, correlated significantly with FEV₁, FVC and FEV₁/FVC, respectively, as measured by spirometry (r = 0.865, 0.751 and 0.57). Among the cardiovascular comorbidities, heart failure and ischaemic heart disease showed slightly stronger associations with airflow limitation (13.8% and 12.5%, respectively).Combination of the PiKo-6 with a COPD questionnaire may be a useful and feasible method of identifying undiagnosed COPD patients attending a cardiovascular outpatient clinic.

Background In patients with pulmonary tuberculosis (TB), shortening the time to sputum culture conversion is desirable to reduce the likelihood of mycobacterial transmission. A persistent positive sputum culture after 2 months of treatment is reported to be associated with the presence of cavitation and the extent of disease on chest X-ray, high colony count, diabetes mellitus, and smoking. However, little is known about factors affecting the time to sputum culture conversion. This study was conducted to evaluate factors affecting the time to sputum culture conversion throughout the course of treatment in adults with pulmonary TB. Methods This study was performed using a database of the medical records of patients with active pulmonary TB who were treated at Hirakata Kohsai Hospital in Hirakata City, Osaka, Japan, from October 2000 to October 2002. Cox proportional-hazards analysis was used to evaluate factors affecting the time to sputum culture conversion after adjusting for potential confounders. Results The data of 86 patients with pulmonary TB were analyzed. The median time to sputum culture conversion was 39 days, and the maximum time was 116 days. The Cox proportional-hazards analysis showed that a higher smear grading (HR, 0.40; 95%CI, 0.23–0.71) and a history of ever smoking (HR, 0.48; 95%CI, 0.25–0.94) were associated with delayed sputum culture conversion. Conclusion High smear grading and smoking prolonged the time to sputum culture conversion in adults with pulmonary TB. To effectively control TB, measures to decrease the cigarette smoking rate should be implemented, in addition to early detection and timely anti-TB treatment.

We report a case of a patient with anti PL-12 antibody accompanied by interstitial pneumonia and severe pulmonary hypertension. At first presentation, hyperkeratotic skin lesions were found, although the diagnosis of CVD was not conclusive. Lung histology showed diffuse fibrosing interstitial pneumonia predominantly in the subpleural regions. During the seven-year follow-up period, severe pulmonary hypertension developed, although the progression of lung fibrosis was relatively limited. Anti-PL12 antibody was detected, and therefore the patient was diagnosed as having antisynthetase syndrome. Lung histology and pulmonary arteriogram suggested that vascular involvement of the disease contributed to the development of severe pulmonary hypertension.

Though IgA nephropathy (IgAN) and sarcoidosis have been reported simultaneously in patients occasionally, it remains controversial whether there is any association between the two. In this report we describe our experience with one definite and two subclinical cases of IgAN diagnosed during the clinical course of sarcoidosis. Our findings suggest a possible association between these disorders, and a higher incidence of subclinical IgAN among sarcoidosis patients than among the general population. We also discuss the common immunological background shared by these two diseases.

Decrease in renal function was investigated in relation to altered metabolism of calcium in patients with sarcoidosis.Fifty consecutive patients with pulmonary sarcoidosis (23 men and 27 women, 47 +/- 15 years as mean +/- SD) were studied on a daily diet consisting of 500 mg of calcium and 1000 mg of phosphorus. Renal functions were evaluated with Z scores of creatinine clearance (Ccr).Decreased renal function (Ccr Z score-1) was detected in 13 out of 50 sarcoidosis patients (26.0%). In seven patients (14.0%) Ccr Z scores were less than -2; relative risk (RR) and 95% confidence interval (95% CI) were 13.9 and 2.97 to 64.7, respectively. Ccr Z score correlated most significantly with serum concentration of ionized calcium (sCa2+) (r = -0.574, 95% CI, -0.735 to -0.352, p0.0001). A stepwise regression analysis adjusting for observation time, serum concentration of calcium and 1,25-Dihydroxyvitamin D, urinary excretion of calcium, and urinary calcium crystals showed that sCa2+, together with angiotensin-converting enzyme activity in serum, was the most contributory variable to decrease in renal function in sarcoidosis patients (R2 = 0.391, p0.0001). A cutoff value of sCa2, 1.30 mmol/L obtained with a discriminant analysis showed 69.2% of sensitivity and 89.2% of specificity for decreased renal function.We reported increased prevalence of decreased renal function among sarcoidosis patients. sCa2+ was a significant index that reflected the alteration of renal function.

Three cases of sarcoidosis with granulomatous interstitial nephritis are reported. Patients were all male and over 50 years of age. They simultaneously had evidence of multiorgan involvement of sarcoidosis including lung and skin and/or eye. In addition, distinct features were found in each case: a granulomatous infiltration mimicking unilateral renal tumor (case 1); renal insufficiency solely due to granulomatous interstitial nephritis (case 2); and renal insufficiency with calcemic nephropathy and granulomatous interstitial nephritis (case 3). Prednisolone therapy resulted in disappearance of the pseudotumor in case 1 and partial improvement of renal function in cases 2 and 3. In cases 2 and 3, however, plasma creatinine did not return to normal values and a second renal biopsy in case 2 demonstrated residual interstitial fibrosis and few granulomas, suggesting that steroid therapy did not achieve complete reversal of changes.

The authors present a rare case where acute respiratory failure occurred after the intravitreal bevacizumab injection for a branch retinal vein occlusion. Chest CT scan showed ground-glass opacity in the bilateral lung fields. The finding of bronchoalveolar lavage fluid revealed alveolar haemorrhage. Corticosteroid therapy resulted in a rapid improvement of respiratory failure. This report suggests that intravitreal injection of bevacizumab may be associated with diffuse alveolar haemorrhage and acute lung injury.

7660 Background: Nedaplatin (CDGP) is a cisplatin derivative developed in Japan. In non-small cell lung cancer (NSCLC), its response as monotherapy has been reported to be 20.5%, while when used in combination with vindesine, its efficacy is similar to cisplatin (CDDP). With respect to adverse effects, it causes less nausea/vomiting and nephrotoxicity compared to CDDP. By these data, we conducted a phase II study of combination treatment with CDGP and docetaxel (TXT) in advanced NSCLC. Methods: Forty six patients (Male/Female 39/7, median age 65 years (40–79), IIIB/IV 20/26) were enrolled from March 2004 to March 2006. Eligibility criteria included signed informed consent, age over 20 and under 80, measurable disease, ECOG PS 0–1, adequate bone marrow reserve, no previous chemotherapy or radiotherapy, and life-expectancy of at least 12 weeks. Treatment consisted of 80 mg/m2 CDGP and 60 mg/m2 TXT on day one with about 1,000 ml of hydration every 3–4 weeks. Results: One hundred and forty four cycles were given to 46 pts (mean cycles 3.1) and the mean dosages actually administered were 75.5±6.1 mg/m2 for CGDP and 57.7±4.6 mg/m2 for TXT. An over all response rate was 52.2% (squamous cell carcinoma 66.7%, adenocarcinoma 44.0%), median survival time was 12 months and 1-year survival rate was 50%. NCI-CTC grades 3–4 leukopenia, neutropenia, nausea/vomiting and appetite loss occurred in 44 (29.2%), 50 (34.7%), 5 (3.5%), 6 (4.2%) cycles, respectively. There was no grade 3–4 anemia, thrombocytopenia and neuropathy. Conclusions: This combination of chemotherapy was well tolerated, and its activity and survival for advanced NSCLC were acceptable. The update data will be presented at the meeting. No significant financial relationships to disclose.

Asthma and chronic obstructive pulmonary disease (COPD) are among the most prevalent lung diseases. In both asthma and COPD, airway inflammation leads to airway remodeling. Parenchyma of the lung is also influenced by disease conditions. Airway wall thickening/lumen narrowing and parenchymal destruction occur in COPD. In asthma, airway remodeling contributes to the lung parenchyma. Computed tomography (CT) has been widely used as an imaging tool for lung diseases. With the technical advancement of CT, together with the development of analysis software, it is now possible to analyze the lung parenchymal change and airway remodeling quantitatively using CT. This article reviews the role of CT in assessing the lung structure and functions of patients with asthma and COPD.