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Background and Objective: Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema. Methods: Based on visual CT assessment, patients with mucus plugs in 0, 1–2 and ≥3 lung segments were assigned to no‐, low‐ and high‐mucus groups. Loss of health‐related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto–Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT. Results: Of 199 and 96 patients in the Kyoto–Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high‐mucus group than in the no‐mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality. Conclusion: Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health‐related independence and mortality in patients with COPD. [ABSTRACT FROM AUTHOR]

Introduction: Lung transplantation (LT) recipients are at risk of bone mineral density (BMD) loss. Pre- and post-LT BMD loss has been reported in some cross-sectional studies; however, there are limited studies regarding the serial BMD change in LT recipients. The aim of this study was to investigate the serial BMD changes and the clinical characteristics associated with BMD decline. Methods: This was a single-center, retrospective observational study. BMD was serially measured in thoracic vertebral bodies (Th4, 7, 10) using computed tomography (CT) before and 3 and 12 months after LT. The frequency of osteoporosis and factors associated with pre-LT osteoporosis and post-LT BMD loss were evaluated. The frequency of post-LT compression fracture and its associated factors were also analyzed. Results: This study included 128 adult LT recipients. LT recipients had decreased BMD (151.8 ± 42.2 mg/mL) before LT compared with age-, sex-, and smoking index-matched controls (176.2 ± 35.7 mg/mL). The diagnosis of COPD was associated with pre-LT osteoporosis. LT recipients experience further BMD decline after transplantation, and the percentage of recipients classified as exhibiting osteoporosis increased from 20% at baseline to 43% at 12 months. Recipients who had been taking no or small doses of glucocorticoids before LT had rapid BMD loss after LT. Early bisphosphonate use (within 3 months) after LT attenuated BMD loss and decreased new-onset compression fracture. Conclusion: LT recipients are at high risk for BMD loss and compression fracture after LT. Early bisphosphonate use may decrease BMD loss and compression fracture. [ABSTRACT FROM AUTHOR]

The factors associated with longitudinal changes in diffusing capacity remain unclear among patients with COPD. Centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are major emphysema subtypes that may have distinct clinical-physiological impacts in these patients. Are CLE and PSE differently associated with longitudinal changes in diffusing capacity and mortality in patients with COPD? This pooled analysis included 399 patients with COPD from two prospective observational COPD cohorts. CLE and PSE were visually assessed on CT scan according to the Fleischner Society statement. The diffusing capacity and transfer coefficient of the lung for carbon monoxide (D lco and K CO) and FEV 1 were evaluated at least annually over a 5-year period. Mortality was recorded over 10 years. Longitudinal changes in FEV 1 , D lco, and K CO and mortality were compared between mild or less severe and moderate or more severe CLE and between present and absent PSE in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The D lco and K CO decline was weakly associated with FEV 1 and greater in GOLD stage 3 or higher than in GOLD stages 1 and 2. Furthermore, moderate or more severe CLE, but not present PSE, was associated with steeper declines in D lco for GOLD stages 1 and 3 or higher and K CO for all GOLD stages independent of age, sex, height, and smoking history. The moderate or more severe CLE, but not present PSE, was associated with additional FEV 1 decline and higher 10-year mortality among patients with GOLD stage 3 or higher. A CT scan finding of moderate or more severe CLE, but not PSE, was associated with a subsequent accelerated impairment in diffusing capacity and higher long-term mortality in severe GOLD stage among patients with COPD. [ABSTRACT FROM AUTHOR]

Background: Physiological and prognostic associations of centrilobular emphysema (CLE) and paraseptal emphysema (PSE) in smokers with and without chronic obstructive pulmonary disease (COPD) have been increasingly recognized, but the associations with extrapulmonary abnormalities, such as muscle wasting, osteoporosis, and cardiovascular diseases, remain unestablished. Objectives: The aim of the study was to investigate whether CLE was associated with extrapulmonary abnormalities independent of concomitant PSE in smokers without airflow limitation. Methods: This retrospective study consecutively enrolled current smokers without airflow limitation who underwent lung cancer screening with computed tomography and spirometry. CLE and PSE were visually identified based on the Fleischner Society classification system. Cross-sectional areas of pectoralis muscles (PM) and adjacent subcutaneous adipose tissue (SAT), bone mineral density (BMD), and coronary artery calcification (CAC) were evaluated. Results: Of 310 current smokers without airflow limitation, 83 (26.8%) had CLE. The PSE prevalence was higher (67.5% vs. 23.3%), and PM area, SAT area, and BMD were lower in smokers with CLE than in those without (PM area (mean), 34.5 versus 38.6 cm2; SAT area (mean), 29.3 versus 36.8 cm2; BMD (mean), 158.3 versus 178.4 Hounsfield unit), while CAC presence did not differ. In multivariable models, CLE was associated with lower PM area but not with SAT area or BMD, after adjusting for PSE presence, demographics, and forced expiratory volume in 1 s. Conclusions: The observed association between CLE and lower PM area suggests that susceptibility to skeletal muscle loss could be high in smokers with CLE even without COPD. [ABSTRACT FROM AUTHOR]

Summary: Nivolumab, a programmed death 1 blockade drug, is used in various types of cancers and can cause a unique immune-related adverse event (irAE). Relapsing polychondritis (RP) is a rare autoimmune disease that mainly involves inflammation of the auricle, nose and airway cartilage. A 72-year-old man with mandibular cancer received nivolumab after surgery for the primary lesion and radiation therapy for lung metastases. He then developed radiation pneumonitis, and prednisolone (PSL) was started. During the tapering of PSL, he developed exertional dyspnea and cough. The condition of mandibular cancer and radiation pneumonitis had not deteriorated. Fluorodeoxyglucose (FDG)-PET/CT showed a thickening of and abnormal FDG uptake in the tracheobronchial and nasal septum cartilage. These characteristic findings were not observed before nivolumab was initiated; thus, we clinically diagnosed the patient as having RP induced by nivolumab. Since the symptoms were mild, the patient's condition was carefully managed with inhaled corticosteroids, and the RP has not progressed thus far. Physicians should be aware that RP can occur as an irAE because RP may progress to serious respiratory symptoms. [ABSTRACT FROM AUTHOR]

Forced expiratory volume in 1 s (FEV1) is a standard physiological index of chronic obstructive pulmonary disease (COPD), but reflects emphysema and vascular abnormalities less sensitively than diffusion capacity for carbon monoxide (DLCO). This study tested whether a disproportionally impaired DLCO relative to FEV1 (FEV1z-score>-3 and DLCOz-score≤-3) is a common functional COPD phenotype associated with distinct clinical and structural features and the prognosis of two cohorts. The cross-sectional analyses of the Korea COPD Subgroup Study (KOCOSS) cohort (multicenter study in Korea) included 743 males with COPD whose DLCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired DLCO relative to FEV1 was observed in 29% and 31% of patients in the KOCOSS and Kyoto University cohorts, respectively. In the multivariable analysis, the disproportionally impaired DLCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV1z-score>-3 and DLCOz-score>-3). In the multivariable Cox proportional hazard model, a higher long-term mortality was observed in the disproportionally impaired DLCO group than in the reference group (hazard ratio [95% confidence interval] = 3.09 [1.52–6.29]) and similar to the DLCOz-score≤-3 and FEV1z-score≤-3 group. The disproportionally impaired DLCO relative to FEV1 is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD. [ABSTRACT FROM AUTHOR]

Background: Low antigravity muscle mass is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, the significance of longitudinal changes in antigravity muscle mass remains unclear in patients with COPD. Objectives: The aims of this study were to investigate the factors associated with the longitudinal loss of antigravity muscles and whether the accelerated loss of these muscles has a negative impact on prognosis. Methods: This study was part of a prospective observational study at Kyoto University. We enrolled stable male patients with COPD who underwent longitudinal quantitative CT analysis of the cross-sectional area of the erector spinae muscles (ESMCSA) at an interval of 3 years. The associations between the rate of change in ESMCSA (%ΔESM) and clinical parameters, such as anthropometry, symptoms, lung function, exacerbation frequency, and all-cause mortality, were investigated. Results: In total, 102 stable male COPD patients were successfully evaluated in this study (71.3 ± 8.3 years, GOLD stage I/II/III/IV = 20/47/28/7 patients). ESMCSA significantly decreased from 30.53 to 28.98 cm2 (p < 0.0001) in 3 years, and the mean %ΔESM was 5.21 ± 7.24%. The rate of survival during the observation period was 85.3% (87/102). Patients with an accelerated decline in ESMCSA (n = 31; more than double the mean rate of decline) had a significantly higher frequency of moderate-to-severe exacerbations during the interval (p = 0.015). They also had significantly worse survival (p = 0.035 by log-rank test). A multivariate Cox proportional hazard model showed that lower ESMCSA and greater %ΔESM decline were independently and significantly associated with mortality. Conclusions: Frequent exacerbations were related to the loss of antigravity muscles in COPD patients. The accelerated loss of antigravity muscles was associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives: The association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA. Methods: We retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT. Results: Adrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (β = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width. Conclusions: Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation. [ABSTRACT FROM AUTHOR]

Background: Distributions of low-attenuation areas in two-dimensional (2-D) CT lung slices are used to quantify parenchymal destruction in patients with COPD. However, these segmental approaches are limited and may not reflect the true three-dimensional (3-D) tissue processes that drive emphysematous changes in the lung. The goal of this study was to instead evaluate distributions of 3-D low-attenuation volumes, which we hypothesized would follow a power law distribution and provide a more complete assessment of the mechanisms underlying disease progression.Methods: CT scans and pulmonary function test results were acquired from an observational database for N = 12 patients with COPD and N = 12 control patients. The data set included baseline and two annual follow-up evaluations in patients with COPD. Three-dimensional representations of the lungs were reconstructed from 2-D axial CT slices, with low-attenuation volumes identified as contiguous voxels < -960 Hounsfield units.Results: Low-attenuation sizes generally followed a power law distribution, with the exception of large, individual outliers termed "super clusters," which deviated from the expected distribution. Super cluster volume was correlated with disease severity (% total low attenuation, ρ = 0.950) and clinical measures of lung function including FEV1 (ρ = -0.849) and diffusing capacity of the lung for carbon monoxide Dlco (ρ = -0.874). To interpret these results, we developed a personalized computational model of super cluster emergence. Simulations indicated disease progression was more likely to occur near existing emphysematous regions, giving rise to a biomechanical, force-induced mechanism of super cluster growth.Conclusions: Low-attenuation super clusters are defining, quantitative features of parenchymal destruction that dominate disease progression, particularly in advanced COPD. [ABSTRACT FROM AUTHOR]

Multiple CT indices are associated with disease progression and mortality in patients with COPD, but which indices have the strongest association remain unestablished. This longitudinal 10-year observational study (n=247) showed that the emphysema severity on CT is more closely associated with the progression of airflow limitation and that a reduction in the cross-sectional area of erector spinae muscles (ESMCSA) on CT is more closely associated with mortality than the other CT indices, independent of patient demographics and pulmonary function. ESMCSA is a useful CT index that is more closely associated with long-term mortality than emphysema and airway disease in patients with COPD. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous distribution of emphysema is a key feature of chronic obstructive pulmonary disease (COPD) patients that typically is evaluated using high-resolution chest computed tomography (HRCT). Oxygen-enhanced pulmonary magnetic resonance imaging (OEMRI) is a new method to obtain information regarding regional ventilation, diffusion, and perfusion in the lung without radiation exposure. We aimed to compare OEMRI with HRCT for the assessment of heterogeneity in COPD patients. Methods: Forty patients with stable COPD underwent quantitative HRCT, OEMRI, and pulmonary function tests, including arterial blood gas analysis. OEMRI was also performed on nine healthy control subjects. We measured the severity of emphysema (percent low attenuation volume; LAV%) in whole lungs and the standard deviations (SDs) of the LAV% values of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal heterogeneity. Similarly, relative enhancement ratios of oxygen (RERs) in whole lungs from OEMRI and SD-RER were analyzed. Results: COPD patients showed a lower mean RER than control subjects (12.6% vs 22.0%, p<0.01). The regional heterogeneity of the RERs was not always consistent with the LAV distribution. Both the HRCT (LAV% and SD-LAV) and the OEMRI (RER and SD-RER) indices were significantly associated with the diffusion capacity (DLCO) and partial pressure of oxygen in arterial blood (PaO2). The PaO2 was associated only with the heterogeneity index of HRCT (SD-LAV) (R2 = 0.39); however, the PaO2 was associated with both the mean RER and heterogeneity (SD-RER) in the multivariate analysis (R2 = 0.38). Conclusions: OEMRI-derived parameters were directly associated with oxygen uptake in COPD patients. Although the OEMRI-derived parameters were not identical to the HRCT-derived parameters, the cranial-caudal heterogeneity in HRCT or OEMRI was complementary to that in evaluations of oxygen uptake in the lungs. Functional imaging seems to provide new insights into COPD pathophysiology without radiation exposure. [ABSTRACT FROM AUTHOR]

Background: The risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD. Methods: We retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy. The existence of ILD in these patients was determined by lung computed tomography findings; 26 patients had ILD. We evaluated the efficacy of nivolumab by measuring the response rate (RR), progression‐free survival (PFS) duration, and lung toxicity by incidence, severity, and outcome of nivolumab‐related ILD. Results: The RR and median PFS of the ILD and non‐ILD groups were 27% versus 13% (P = 0.078) and 2.7 (95% confidence interval [CI], 1.7–5.3) versus 2.9 months (95% CI 2.1–3.4; P = 0.919), respectively. The incidences of total and severe nivolumab‐related pneumonitis were significantly higher in the ILD group than in the non‐ILD group (31% vs. 12%, P = 0.014 and 19% vs. 5%, P = 0.022, respectively). No death from nivolumab‐related pneumonitis occurred. Over 50% of the patients in both groups with nivolumab‐related pneumonitis showed improvement over time. Conclusion: Relative to the non‐ILD group, nivolumab‐related pneumonitis was observed more frequently in the ILD group; however, most cases were manageable. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is an established factor in the pathogenesis and exacerbation of fatty liver disease. However, randomized controlled trials have failed to demonstrate decreases in liver fat content in OSA patients by continuous positive airway pressure (CPAP) performed for several months. The aim of this study is to investigate the impact of long-term CPAP therapy on liver fat content in OSA patients with fatty liver. Liver fat content in 61 male OSA patients was evaluated by computed tomography performed because of abdominal obesity before and after CPAP initiation. At baseline, there were 25 participants with fatty liver. Their apnea-hypopnea index and percent sleep time with oxygen saturation < 90% were greater than those in the 36 participants who did not have fatty liver (52.3 vs. 41.8/h and 30.4 vs. 14.8%, respectively). The average therapy duration was 31 months. In the analysis of the entire participant group, liver fat content did not change after CPAP therapy. In those without fatty liver, liver fat content increased accompanied by increases in BMI, whereas in the participants with fatty liver, liver fat content decreased despite stable BMI, abdominal fat distribution, and insulin resistance. In male OSA patients with abdominal obesity, decreases in liver fat content were observed after long-term CPAP therapy only when fatty liver was present at baseline. This implies that there are some conditions, such as OSA-related hypoxemia and others, which may exacerbate fatty liver and that fatty liver may improve with CPAP therapy. [ABSTRACT FROM AUTHOR]

Many groups developed the methods to quantitatively analyze low attenuation area (LAA) on chest CT in patients with cystic lung diseases. Especially in COPD, it was reported that the cumulative size distribution of LAA clusters follows a power law characterized by the exponent D, which reflect the fractal dimension of terminal airspace geometry. We hypoyhesized that the quantitative charateristics of LAA clusters including fractal property might indicate the different features of the progression of cysts in cystic lung diseases. The aim of this study was to apply the CT image-based method of characterizing the size distribution of LAA clusters for lymphangioleiomyomatosis (LAM) and Birt-Hogg-Dubé syndrome (BHDS) to disclose their features of the progression of pulmonary cysts. 40 patients with COPD, 52 patients with LAM, and 18 patients with BHDS who had undergone CT scans at our institute between January 2002 and August 2009 were included. Differences among these diseases in the quantitative characteristics of LAA clusters {i.e., extent, number, size, fractal property, and the relationship between these quantitatives} were assessed. The Chi-sqsuare test, unpaired t-test, and one-way analyses of variance with Tukey post-hoc tests were used to compare groups, spline model with an interaction terms were used to assess the relationship between extent and number, and exponential regression model was used to assess the relationship between extent and size. Statistically significant differences separated the three diseases in extent and number (P < 0.001). Number was significantly correlated with extent in COPD (P < 0.001), but was not so in LAM and BHDS when extent exceeded 11.5% and 20.8%, respectively. Size was significantly correlated with extent in COPD and LAM (P < 0.001), but was not so in BHDS. The percentage of CT images with fractal property was higher in COPD than that in LAM and BHDS (95.8%, 92.9% and 63.0%, respectively). In conclusion, our study has demonstrated for the first time the different characteristics of the size distribution of LAA clusters among COPD, LAM and BHDS, and indicated that this method is useful for exploration of the pathophysiology in cystic lung diseases. [ABSTRACT FROM AUTHOR]

Rationale: Loss of skeletal muscle mass and physical inactivity are important manifestations of chronic obstructive pulmonary disease (COPD), and both are closely related to poor prognoses in patients with COPD. Antigravity muscles are involved in maintaining normal posture and are prone to atrophy with inactivity. The erector spinae muscles (ESM) are one of the antigravity muscle groups, and they can be assessed by chest computed tomography (CT). Objectives: We hypothesized that the cross-sectional area of ESM (ESMCSA) visualized on chest CT images may serve as a predictor of mortality in patients with COPD. Methods: This study was part of the prospective observational study undertaken at Kyoto University Hospital. ESMCSA was measured on a single-slice axial CT image at the level of the 12th thoracic vertebra in patients with COPD. The cross-sectional area of the pectoralis muscles (PMCSA) was also measured. We evaluated the relationship between ESMCSA and clinical parameters, including mortality, in patients with COPD. Age- and height-matched smoking control subjects were also evaluated. Measurements and Main Results: In total, 130 male patients and 20 smoking control males were enrolled in this study. ESMCSA was significantly lower in patients with COPD than in the smoking control subjects and was significantly correlated with disease severity. There was a significant but only moderate correlation between ESMCSA and PMCSA. ESMCSA was significantly correlated with previously reported prognostic factors, such as body mass index, dyspnea (modified Medical Research Council dyspnea scale score), FEV1 percent predicted value, inspiratory capacity to total lung capacity ratio, and emphysema severity (percentage of the lung field occupied by low attenuation area). Compared with PMCSA, ESMCSA was more strongly associated with mortality in patients with COPD. Stepwise multivariate Cox proportional hazards analysis revealed that, among these known prognostic factors, ESMCSA was the strongest risk factor for mortality (hazard ratio, 0.85; 95% confidence interval, 0.79-0.92; P < 0.001) and mMRC dyspnea scale score was an additional factor (hazard ratio, 2.35; 95% confidence interval, 1.51-3.65; P < 0.001). Conclusions: ESMCSA assessed by chest CT may be a valuable clinical parameter, as ESACSA correlates significantly with physiological parameters, symptoms, and disease prognosis. [ABSTRACT FROM AUTHOR]

Objectives. 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was reported to be useful for monitoring immunoglobulin G4-related disease (IgG4-RD); however, a quantitative FDG-PET/CT analysis such as total lesion glycolysis (TLG) has not yet been conducted. This study aimed to investigate whether TLG would correlate with serum markers in IgG4-RD, and the utility of TLG for disease monitoring. Methods. This retrospective study included 17 patients (12 men; median age, 62 years) who were followed up at Kyoto University Hospital and underwent FDG-PET/CT from April 2009 to November 2013. TLG was calculated for the involved lesions. Correlations between serum markers [IgG4, soluble IL-2 receptor (sIL-2R), lactate dehydrogenase (LDH), and C-reactive protein (CRP)] and TLG concomitant with FDG-PET/CT scans were investigated. Serial changes in TLG were assessed in patients who underwent follow-up FDG-PET/CT ( n = 6). Results. The calculated median (IQL) TLG value was 154.8 (63.7-324.4). A significant correlation was found between the sIL-2R level and TLG ( P = 0.001, rs = 0.763). In contrast, no correlations were found between the IgG4, LDH, or CRP levels and TLG. Increased or decreased TLG corresponded with clinical disease improvement or worsening. Conclusions. TLG correlated significantly with the serum sIL-2R level and may be useful for disease monitoring in IgG4-RD. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT) assessment of air trapping has been considered useful as a measure of small airway disease. Mean lung density (MLD) and the percentage of the lung field occupied by low attenuation area (LAA%) can be evaluated automatically, and their expiratory/inspiratory (E/I) ratios correlate with asthma severity and spirometry parameters. However, mosaic attenuation, another indicator of air trapping, has been assessed visually, and its functional relevance remains controversial. Objectives: This retrospective study was conducted to correlate mosaic attenuation, which was assessed visually and automatically, and the E/I ratios of MLD and LAA% (defined as areas <-960 Hounsfield units) with clinical and physiological variables, including impulse oscillometry (IOS) indices. Material and Methods: In 36 nonsmoking patients with stable asthma, the lungs were scanned at full inspiration and full expiration. Mosaic attenuation was measured visually and automatically, by counting areas with CT values higher than the surrounding areas. MLD and LAA% were measured using our validated method. Spirometry, IOS, exhaled NO and the sputum eosinophil count were evaluated. Results: The automatic results and visual scores of mosaic attenuation correlated well on expiratory scans (r = 0.894) and to a lesser degree on inspiratory scans (r = 0.629; p < 0.0001 for both). However, only the E/I ratios of MLD and LAA% correlated with forced expiratory volume in 1 s/forced vital capacity of spirometry and the IOS indices of resistance from 5 to 20 Hz and the integrated area of low-frequency reactance. Conclusions: Our automatic method for analysis of mosaic attenuation is likely useful, but the results themselves may not be reflecting small airway involvement of asthma, unlike the E/I ratios of MLD and LAA%. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Health-related quality of life (HRQoL) is important in the management of chronic obstructive pulmonary disease (COPD). In patients with emphysema, lung hyperinflation identified radiologically as shortening and flattening of the diaphragm is associated with impaired HRQoL. It remains unclear whether shortening of the diaphragm and/or alteration in chest wall shape are associated with reduced pulmonary function and HRQoL. Methods: Pulmonary function testing and chest computed tomography (CT) were performed, and the St. George's Respiratory Questionnaire (SGRQ) was administered to 123 patients with COPD. Using CT images, the ratio of volume of lung region adjacent to the diaphragm dome to total lung volume (DLV%) was evaluated as a novel CT index, and conventional indices, including percent low attenuation volume (LAV%), wall area percent (WA%), total lung volume and diaphragm length (Ldi) were calculated. Results: DLV% was significantly correlated with Ldi. DLV% and Ldi were inversely correlated with lung hyperinflation, assessed as the ratio of residual volume to total lung capacity, independent of LAV% and WA%. Unlike Ldi, DLV% was inversely associated with all components and total scores for the SGRQ, independent of the severity of emphysema and airflow limitation. Conclusions: Reduced lung volume around the diaphragm correlated with lung hyperinflation and HRQoL, independent of emphysema severity. This needs to be verified in additional studies. [ABSTRACT FROM AUTHOR]

Abstract: Backgrounds: Since Birt–Hogg–Dubé syndrome (BHDS) and lymphangioleiomyomatosis (LAM) share some clinical manifestations (multiple pulmonary cysts with pneumothorax, renal tumors, and sometimes skin lesions), the differential diagnosis of the two diseases becomes problem especially in female patients. This study aims to quantify pulmonary cysts in computed tomography (CT) of females with BHDS and those with LAM and also to identify the independent parameters for differentiating the two diseases. Methods: Fourteen patients with BHDS and 52 with LAM were studied. In CT scans, lung fields were defined as areas with fewer than −200 Hounsfield units (HU) and pulmonary cysts as areas consisting of 10 or more consecutive pixels with fewer than −960 HU. The extent, number, size and circularity of cysts were calculated by using hand-made software and compared between the two diseases. Moreover, the lung fields were divided into six zones and analyzed for the distribution of cysts. Finally, a stepwise discriminant analysis employing quantitative measurements of cysts and clinical features was performed. Results: The two diseases were significantly different in all quantitative measurements of cysts. Stepwise discriminant analysis accepted the following four variables: the family history of pneumothorax within the second degree relatives, lower-medial zone predominance of cysts, diffusing capacity and mean size of cysts in this order. Conclusion: The quantitative characteristics of pulmonary cysts are significantly different between BHDS and LAM. The independent parameters for differentiating the two diseases are the family history of pneumothorax, zonal predominance of cysts, diffusing capacity and size of cysts. [Copyright &y& Elsevier]

Background: It was previously reported that visual scores of the lung opacities were associated with lung function in patients with sarcoidosis. However, there are no reports on the evaluation of airway dimensions or lung density by computed tomography (CT) in sarcoidosis patients. Objectives: The aim of this study was to investigate whether airway dimensions and lung densities assessed by CT associate with pulmonary function in patients with sarcoidosis. Methods: CT scanning was performed in 43 sarcoidosis patients and lung densities were measured using in-house software. Means and standard deviations of lung density, kurtosis and skewness of lung density histograms were calculated. Tracheal area and airway wall area/total airway area (WA%) of the right apical bronchus were also measured. Pulmonary function tests were performed on the same day. Results: Increased standard deviation of lung density and decreased kurtosis and skewness of lung density histograms were all associated with decreased total lung capacity, vital capacity and diffusion capacity. Increased standard deviation of lung density was also associated with decreased percentages of forced expiratory volume in 1 s and peak expiratory flow (%PEF). There was a positive correlation between tracheal area corrected by body surface area and %PEF, and negative correlation between WA% and %PEF. Stepwise regression analysis showed that increased standard deviation of lung density and decreased tracheal area were independently associated with lower %PEF. Conclusions: Thus, in sarcoidosis, densitometric parameters reflect restrictive lung function impairment. In addition to parenchymal lesions, it is concluded that the luminal area of the central airways also affects PEF. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Remaining lung tissue after pulmonary resection can expand without decline in structural complexity and compensate for functional loss, showing morphological and functional reserves. However, the distribution of these reserves is unknown. This study examined the heterogeneity of morphological and functional reserves of the remaining lung tissue. We retrospectively analyzed 53 donors who underwent right lower lobectomy for living-donor lobar lung transplantation. We examined morphometric changes in computed tomography images from 3 to 12 months after lobectomy. We assessed lung volume and structural complexity expressed as the fractal dimension. We also assessed effective lung volume (the volume of the lung with intermediate density) and volumetric fluctuation during respiration. Changes were compared between the right upper lobe, middle lobe, and left lung. The expansion of lung tissue was greater in the middle lobe (130.9% ± 19.7%) than in the upper lobe (109.7% ± 9.2%; P <.001). The fractal dimension declined in the upper lobe (P <.001) but was maintained in the middle lobe (P =.39). The increase in effective lung volume was larger in the middle lobe (97.2 ± 73.5 mL) than in the upper lobe (62.7 ± 87.1 mL; P <.001), but not significantly different from that of the left lung (55.8 ± 186.3 mL; P =.052). A similar pattern was seen in respiratory fluctuation. Morphological and functional changes in lung tissue remaining after pulmonary resection were heterogeneous. The right middle lobe demonstrated morphological and functional reserves after right lower lobectomy. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite clinical implications, the pathogenesis of mucus plugging in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) remains unclear. We hypothesized that distinct airway microbiomes might affect mucus plugging differently among ACO, asthma, and COPD and among different extents of airway eosinophilic inflammation. The sputum microbiome, sputum cell differential count, and mucus plug score on computed tomography were cross-sectionally evaluated in patients with chronic airflow limitation. Patients with ACO, asthma, or COPD were enrolled (n = 56, 10, and 25). Higher mucus plug scores were associated with a greater relative abundance of the phylum Proteobacteria (rho = 0.29) only in patients with ACO and a greater relative abundance of the phylum Actinobacteria (rho = 0.46) only in patients with COPD. In multivariable models including only patients with ACO, the presence of mucus plugs was associated with a greater relative abundance of the phylum Proteobacteria and the genus Haemophilus, independent of smoking status, airflow limitation, and emphysema severity. Moreover, the mucus score was associated with a greater relative abundance of the genus Streptococcus (rho = 0.46) in patients with a high sputum eosinophil count (n = 22) and with that of the genus Haemophilus (rho = 0.46) in those with a moderate sputum eosinophil count (n = 26). The associations between mucus plugging and the microbiome in ACO differed from those in COPD and asthma. Greater relative abundances of the phylum Proteobacteria and genus Haemophilus may be involved in mucus plugging in patients with ACO and moderate airway eosinophilic inflammation. [ABSTRACT FROM AUTHOR]

Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20–35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers. [ABSTRACT FROM AUTHOR]

Background: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT).Methods: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated.Results: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07).Conclusions: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance. [ABSTRACT FROM AUTHOR]

The physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical–physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma. A total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT. More mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics. The association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma. [ABSTRACT FROM AUTHOR]

[Display omitted] • HRCT images of 207 patients were analysed using AI-based software to predict SRP. • Reticulation and honeycombing volume differed among patients with and without SRP. • Br-volume & NL-D mean were used to create a SRP predictive model. • The model categorized SRP risk into high, intermediate, and low. • Incidence rates: 62.5, 38.4, 7.5% (training) & 50.0, 27.3, 5.0% (testing) groups. Symptomatic radiation pneumonitis (SRP) is a complication of thoracic stereotactic body radiotherapy (SBRT). As visual assessments pose limitations, artificial intelligence-based quantitative computed tomography image analysis software (AIQCT) may help predict SRP risk. We aimed to evaluate high-resolution computed tomography (HRCT) images with AIQCT to develop a predictive model for SRP. AIQCT automatically labelled HRCT images of patients treated with SBRT for stage I lung cancer according to lung parenchymal pattern. Quantitative data including the volume and mean dose (D mean) were obtained for reticulation + honeycombing (Ret + HC), consolidation + ground-glass opacities, bronchi (Br), and normal lungs (NL). After associations between AIQCT's quantified metrics and SRP were investigated, we developed a predictive model using recursive partitioning analysis (RPA) for the training cohort and assessed its reproducibility with the testing cohort. Overall, 26 of 207 patients developed SRP. There were significant between-group differences in the Ret + HC, Br-volume, and NL-D mean in patients with and without SRP. RPA identified the following risk groups: NL-D mean ≥ 6.6 Gy (high-risk, n = 8), NL-D mean < 6.6 Gy and Br-volume ≥ 2.5 % (intermediate-risk, n = 13), and NL-D mean < 6.6 Gy and Br-volume < 2.5 % (low-risk, n = 133). The incidences of SRP in these groups within the training cohort were 62.5, 38.4, and 7.5 %; and in the testing cohort 50.0, 27.3, and 5.0 %, respectively. AIQCT identified CT features associated with SRP. A predictive model for SRP was proposed based on AI-detected Br-volume and the NL-D mean. [ABSTRACT FROM AUTHOR]

Purpose: Disease in small airways <2 mm in diameter is a major pathology of chronic obstructive pulmonary disease (COPD). However, compared to airways <1 mm in diameter, the pathophysiological role of airways 1-2 mm in diameter remains unclear. This study analysed phantom and human COPD data to test the hypothesis that ultra-high-resolution computed tomography (U-HRCT) can accurately measure peripheral airways that are difficult to measure with conventional CT.Method: The lower limit of lumen sizes measurable on U-HRCT was determined using phantom tubes. In the cross-sectional data of 110 males with COPD who underwent U-HRCT (1024 × 1024 matrix, 0.25 mm slice thickness) and spirometry, all 3rd (segmental) to 6th generation airways of the right apical and basal posterior bronchus (RB1 and RB10) were analysed.Results: The errors in measuring the lumen area (LA) of phantom tubes ≥1.3 and 1.0 mm in diameter were within ±10 and -24%, respectively. The internal diameters for 70 and 62% of the 6th generation RB1 and RB10 airways were <2 mm. The numbers of 6th generation RB1 and RB10 airways decreased as the airflow limitation severity increased. Among the mean LA and sum of LA(sum-LA) of the 3rd to 6th generation airways, the sum-LA of the 6th generation had the largest impact on airflow limitation.Conclusions: U-HRCT enables accurate and direct evaluation of peripheral airways 1-2 mm in diameter. The 6th generation airways are commonly <2 mm in diameter, and the sum-LA can be a useful CT biomarker that reflects airflow limitation in COPD. [ABSTRACT FROM AUTHOR]