Percent Wall Research Articles

GOLD-Grade Specific Disease Characterization and Phenotyping of COPD Using Quantitative Computed Tomography in the Nationwide COSYCONET Multicenter Trial in Germany

Introduction: The aim of this study was to apply quantitative computed tomography (QCT) for GOLD-grade specific disease characterization and phenotyping of air-trapping, emphysema, and airway abnormalities in patients with chronic obstructive pulmonary disease (COPD) from a nationwide cohort study. Methods: As part of the COSYCONET multicenter study, standardized CT in ex- and inspiration, lung function assessment (FEV1/FVC), and clinical scores (BODE index) were prospectively acquired in 525 patients (192 women, 327 men, aged 65.7 ± 8.5 years) at risk for COPD and at GOLD1–4. QCT parameters such as total lung volume (TLV), emphysema index (EI), parametric response mapping (PRM) for emphysema (PRMEmph) and functional small airway disease (PRMfSAD), total airway volume (TAV), wall percentage (WP), and total diameter (TD) were computed using automated software. Results: TLV, EI, PRMfSAD, and PRMEmph increased incrementally with each GOLD grade (p < 0.001). Aggregated WP5–10 of subsegmental airways was higher from GOLD1 to GOLD3 and lower again at GOLD4 (p < 0.001), whereas TD5–10 was significantly dilated only in GOLD4 (p < 0.001). Fifty-eight patients were phenotyped as “non-airway non-emphysema type,” 202 as “airway type,” 96 as “emphysema type,” and 169 as “mixed type.” FEV1/FVC was best in “non-airway non-emphysema type” compared to other phenotypes, while “mixed type” had worst FEV1/FVC (p < 0.001). BODE index was 0.56 ± 0.72 in the “non-airway non-emphysema type” and highest with 2.55 ± 1.77 in “mixed type” (p < 0.001). Conclusion: QCT demonstrates increasing hyperinflation and emphysema depending on the GOLD grade, while airway wall thickening increases until GOLD3 and airway dilatation occur in GOLD4. QCT identifies four disease phenotypes with implications for lung function and prognosis.

Abstract TP143: Longitudinal Evaluation of Vessel Wall MRI Demonstrates Bilaterally Symmetric Evolution of Carotid Atherosclerosis

Introduction: Carotid atherosclerosis is a leading cause of stroke worldwide. Previous studies demonstrated bilateral symmetry in atherosclerotic plaque burden and calcification scores. By leveraging longitudinal 3D vessel wall MRI, this study aims to investigate if there is a symmetrical trend of bilateral plaque progression. Methods: Asymptomatic patients with confirmed carotid stenosis were prospectively recruited in the study. Subjects underwent baseline and follow-up 3D vessel wall imaging for a time span up to 8 years. A deep learning-based pipeline was used to bilaterally segment the carotid lumen and vessel wall on axial image slices. Within each artery, the range of slices with wall thickness &gt; 2mm on any scan was included as potential atherosclerotic plaque. Plaque burden, positively associated with stroke risk, was defined as the percent wall volume (wall volume / total vessel volume х 100%). For each plaque, a linear model was fitted across all available time points to determine the growth rate of plaque burden. We used generalized estimating equation-based linear regression models to evaluate associations of the growth rate of each side with the contralateral side, adjusted for clinical risk factors and medications. Effect sizes were summarized using the partial correlation coefficient. Results: 20 subjects (mean age 73.5 years, 3 females, 14 on statins) who underwent at least three scans with bilateral carotid plaque were included in the analysis. Each subject underwent an average of 4.8 scans over 5.2 years. Overall, the plaque growth rate of one side was moderately correlated with the contralateral side (r=0.50, p=0.004), even after adjusting for age, sex and statins use. Then, for each subject, the larger of the two plaques at baseline (left or right side) was identified. The growth rate of the larger plaque was also predictive of the growth rate of the smaller plaque over the same time period (r=0.66, p=0.004). Conclusion: The systemic nature of atherosclerotic disease entails an association in symmetrical disease evolution for left and right carotid arteries. In bilaterally diseased patients, the longitudinal monitoring of the more advanced carotid lesion may provide prognostic information on the less advanced contralateral plaque.

Qualitative and quantitative evaluation of computed tomography changes in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: a retrospective observational study.

Introduction: The availability of highly effective triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination therapy with elexacaftor-tezacaftor-ivacaftor (ETI) has improved pulmonary outcomes and quality of life of people with cystic fibrosis (pwCF). The aim of this study was to assess computed tomography (CT) changes under ETI visually with the Brody score and quantitatively with dedicated software, and to correlate CT measures with parameters of clinical response. Methods: Twenty two adult pwCF with two consecutive CT scans before and after ETI treatment initiation were retrospectively included. CT was assessed visually employing the Brody score and quantitatively by YACTA, a well-evaluated scientific software computing airway dimensions and lung parenchyma with wall percentage (WP), wall thickness (WT), lumen area (LA), bronchiectasis index (BI), lung volume and mean lung density (MLD) as parameters. Changes in CT metrics were evaluated and the visual and quantitative parameters were correlated with each other and with clinical changes in sweat chloride concentration, spirometry [percent predicted of forced expiratory volume in one second (ppFEV1)] and body mass index (BMI). Results: The mean (SD) Brody score improved with ETI [55 (12) vs. 38 (15); p < 0.001], incl. sub-scores for mucus plugging, peribronchial thickening, and parenchymal changes (all p < 0.001), but not for bronchiectasis (p = 0.281). Quantitatve WP (p < 0.001) and WT (p = 0.004) were reduced, conversely LA increased (p = 0.003), and BI improved (p = 0.012). Lung volume increased (p < 0.001), and MLD decreased (p < 0.001) through a reduction of ground glass opacity areas (p < 0.001). Changes of the Brody score correlated with those of quantitative parameters, exemplarily WT with the sub-score for mucus plugging (r = 0.730, p < 0.001) and peribronchial thickening (r = 0.552, p = 0.008). Changes of CT parameters correlated with those of clinical response parameters, in particular ppFEV1 with the Brody score (r = -0.606, p = 0.003) and with WT (r = -0.538, p = 0.010). Discussion: Morphological treatment response to ETI can be assessed using the Brody score as well as quantitative CT parameters. Changes in CT correlated with clinical improvements. The quantitative analysis with YACTA proved to be an objective, reproducible and simple method for monitoring lung disease, particularly with regard to future interventional clinical trials.

GOLD stage-specific phenotyping of emphysema and airway disease using quantitative computed tomography.

In chronic obstructive pulmonary disease (COPD) abnormal lung function is related to emphysema and airway obstruction, but their relative contribution in each GOLD-stage is not fully understood. In this study, we used quantitative computed tomography (QCT) parameters for phenotyping of emphysema and airway abnormalities, and to investigate the relative contribution of QCT emphysema and airway parameters to airflow limitation specifically in each GOLD stage. Non-contrast computed tomography (CT) of 492 patients with COPD former GOLD 0 COPD and COPD stages GOLD 1-4 were evaluated using fully automated software for quantitative CT. Total lung volume (TLV), emphysema index (EI), mean lung density (MLD), and airway wall thickness (WT), total diameter (TD), lumen area (LA), and wall percentage (WP) were calculated for the entire lung, as well as for all lung lobes separately. Results from the 3rd-8th airway generation were aggregated (WT3-8, TD3-8, LA3-8, WP3-8). All subjects underwent whole-body plethysmography (FEV1%pred, VC, RV, TLC). EI was higher with increasing GOLD stages with 1.0 ± 1.8% in GOLD 0, 4.5 ± 9.9% in GOLD 1, 19.4 ± 15.8% in GOLD 2, 32.7 ± 13.4% in GOLD 3 and 41.4 ± 10.0% in GOLD 4 subjects (p < 0.001). WP3-8 showed no essential differences between GOLD 0 and GOLD 1, tended to be higher in GOLD 2 with 52.4 ± 7.2%, and was lower in GOLD 4 with 50.6 ± 5.9% (p = 0.010 - p = 0.960). In the upper lobes WP3-8 showed no significant differences between the GOLD stages (p = 0.824), while in the lower lobes the lowest WP3-8 was found in GOLD 0/1 with 49.9 ± 6.5%, while higher values were detected in GOLD 2 with 51.9 ± 6.4% and in GOLD 3/4 with 51.0 ± 6.0% (p < 0.05). In a multilinear regression analysis, the dependent variable FEV1%pred can be predicted by a combination of both the independent variables EI (p < 0.001) and WP3-8 (p < 0.001). QCT parameters showed a significant increase of emphysema from GOLD 0-4 COPD. Airway changes showed a different spatial pattern with higher values of relative wall thickness in the lower lobes until GOLD 2 and subsequent lower values in GOLD3/4, whereas there were no significant differences in the upper lobes. Both, EI and WP5-8 are independently correlated with lung function decline.

Peroxisome proliferator-activated receptor gamma (PPARγ) activation: a potential treatment for ascites syndrome in broiler chickens

Ascites (serous fluid accumulation in the abdominal cavity) has been observed worldwide in fast growing broilers. Pulmonary vascular remodeling is an important pathological feature of broiler ascites syndrome. Peroxisome proliferators-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) are expressed in pulmonary vascular endothelial cells and vascular smooth muscle cells (VSMC) where they participate in the regulation of normal pulmonary vascular function. The objective of the present study was to investigate the effects of omega-3 fatty acids (found in fish oil) and pioglitazone (PIO) as natural and synthetic PPARγ ligands supplementation on PPARγ and PGC-1α expression in the prevention of pulmonary arterial hypertension (PAH) syndrome in broiler chickens. The experiment was conducted with 4 treatment groups: 1) negative control, normal temperature conditions with basal diet; 2) positive control, low-temperature conditions with basal diet; 3) positive control+10 mg PIO/kg of weight/d and 4) positive control+1% FO. Each treatment had 5 replicates. Ascites heart index (RV/TV) was significantly (P < 0.05) reduced in chickens receiving FO (0.20) and PIO (0.21) compared to the positive control group (0.26). The addition of PIO in broilers under cold-induced ascites significantly increased the expression of PPARγ (9.44) and PGC-1α (5.81) genes in lung tissue compared to the negative control group (1.03, P < 0.05). Proliferative indexes of VSMC in pulmonary arteries such as PMT, PIT, and percentage wall thickness were significantly elevated in positive control group, indicating that pulmonary vascular remodeling occurred following VSMC proliferation in ascites. The vessel internal diameter was increased in FO and PIO groups. Based on these results, activation and expression of PPARγ and PGC-1α genes as a critical regulator of pulmonary artery smooth muscle cell using ligands, especially PIO, can be effective in reducing the incidence of PAH in broiler chickens.

Effects of moderate dose rosuvastatin on carotid plaque in patients with diabetes mellitus evaluated by magnetic resonance imaging

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm3 vs. 75.76 (48.20, 115.64) mm3, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm3 vs. 72.49 (51.91, 199.59) mm3, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm3) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.

Efficacy of a house dust mite sublingual immunotherapy tablet as add-on dupilumab in asthma with rhinitis

BackgroundHDM SLIT is one of the disease-modifying treatment for allergic asthma, and has demonstrated efficacy in clinical trials. Dupilumab, blocks IL-4 and IL-13 signaling, key drivers of type 2 inflammation, and is approved for patients with uncontrolled, moderate-to-severe asthma. The aim of this study was to evaluate outcomes after HDM SLIT initiation in asthma with rhinitis not optimally controlled with dupilumab in a real-world setting. MethodsAt baseline and 48 weeks after treatment, asthma control questionnaire (ACQ)-5, asthma quality of life questionnaire (AQLQ) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were assessed. Spirometry, type 2 inflammatory biomarkers and quantitative computed tomographic parameters of airway remodeling were also collected. ResultsOf 47 patients received HDM SLIT and 41 completed the study. Combined HDM SLIT and dupilumab improved ACQ-5 (p < 0.05), AQLQ (p < 0.05), RQLQ (p < 0.05), and increased lung function and reduced FeNO (p < 0.05) and airway percentage wall area, and wall thickness (each, p < 0.05). The change in ACQ-5 and AQLQ score correlated with both changes in FeNO and FEV1 percent predicted. Multiple regression analysis showed that the change in FEV1 percent predicted was independent factor for improvement of AQLQ (r2 = 0.510, p = 0.012). Based on ROC analysis for predicting SLIT responders, the baseline area under the curves in serum HDM specific-IgE, total IgE and FEV1 percent predicted were high (>0.8). ConclusionsThese results support the benefits of adding HDM SLIT to pharmacotherapy plus dupilumab in uncontrolled asthma with rhinitis.

Bronchial wall parameters on CT in healthy never-smoking, smoking, COPD, and asthma populations: a systematic review and meta-analysis

ObjectiveResearch on computed tomography (CT) bronchial parameter measurements shows that there are conflicting results on the values for bronchial parameters in the never-smoking, smoking, asthma, and chronic obstructive pulmonary disease (COPD) populations. This review assesses the current CT methods for obtaining bronchial wall parameters and their comparison between populations.MethodsA systematic review of MEDLINE and Embase was conducted following PRISMA guidelines (last search date 25th October 2021). Methodology data was collected and summarised. Values of percentage wall area (WA%), wall thickness (WT), summary airway measure (Pi10), and luminal area (Ai) were pooled and compared between populations.ResultsA total of 169 articles were included for methodologic review; 66 of these were included for meta-analysis. Most measurements were obtained from multiplanar reconstructions of segmented airways (93 of 169 articles), using various tools and algorithms; third generation airways in the upper and lower lobes were most frequently studied. COPD (12,746) and smoking (15,092) populations were largest across studies and mostly consisted of men (median 64.4%, IQR 61.5 – 66.1%). There were significant differences between populations; the largest WA% was found in COPD (mean SD 62.93 ± 7.41%, n = 6,045), and the asthma population had the largest Pi10 (4.03 ± 0.27 mm, n = 442). Ai normalised to body surface area (Ai/BSA) (12.46 ± 4 mm2, n = 134) was largest in the never-smoking population.ConclusionsStudies on CT-derived bronchial parameter measurements are heterogenous in methodology and population, resulting in challenges to compare outcomes between studies. Significant differences between populations exist for several parameters, most notably in the wall area percentage; however, there is a large overlap in their ranges.Key Points• Diverse methodology in measuring airways contributes to overlap in ranges of bronchial parameters among the never-smoking, smoking, COPD, and asthma populations.• The combined number of never-smoking participants in studies is low, limiting insight into this population and the impact of participant characteristics on bronchial parameters.• Wall area percent of the right upper lobe apical segment is the most studied (87 articles) and differentiates all except smoking vs asthma populations.

The effect of transglutaminase-2 inhibitor on pulmonary vascular remodeling in rats with pulmonary arterial hypertension

ABSTRACT To investigate the relationship between transglutaminase type 2 (TG2) and pulmonary vascular remodeling in the formation of pulmonary arterial hypertension (PAH), and to investigate the effect of the inhibitor cystamine dihydrochloride on pulmonary vascular remodeling in rats with PAH. Thirty healthy male Sprague Dawley rats were randomly divided into a control group, a PAH model group, and an intervention group. The mean pulmonary artery pressure (mPAP), the right ventricular hypertrophy index (RVHI), the percentage wall thickness of the pulmonary artery (WT%), and the degree of neointimal proliferation were measured, and the pathological changes in the pulmonary tissues were observed.Messenger ribonucleic acid (mRNA) and protein expressions of TG2, 5-hydroxytryptamine transporter (5-HTT), and Rho-associated protein kinase 2 (ROCK2) in the pulmonary tissues of the three groups of rats were detected. Compared with the control group, the mPAP, RVHI, and WT% were significantly higher in the model group, the degree of neointimal proliferation was significantly increased, and the mRNA and protein expressions of TG2, 5-HTT, and ROCK2 in the pulmonary tissue were significantly increased. Compared with the model group, the mPAP, RVHI, WT%, and the degree of neointimal proliferation were significantly lower in the intervention group, as were the mRNA and protein expressions of TG2, 5-HTT, and ROCK2 in the pulmonary tissue. The TG2 inhibitor cystamine dihydrochloride can prevent the formation of PAH to some extent. This might be due to the inhibition of the TG2 activity, 5-HTT expression, and possibly the inhibition of RhoA/ROCK signaling pathway activation.

Rooting Volume Impacts Growth, Coverage and Thermal Tolerance of Green Façade Climbing Plants

Green façades can provide cooling benefits through the shading of walls, evapotranspiration, and insulation. These benefits depend on good plant coverage and tolerance of heat stress. This requires sufficient rooting volume for plant growth and an adequate supply of moisture. On high-rise buildings, plants can be constrained by small rooting volumes due to engineering weight limits and cost. We assessed effects of rooting volume (21, 42, and 63 L) on the growth and coverage of Akebia quinata and Pandorea pandorana and leaf stress (chlorophyll fluorescence) in response to increasing air temperatures. We showed that 42 and 63 L rooting volumes significantly increased early plant growth and the percentage wall coverage for both species. Specific leaf area was significantly greater when grown in 63 L compared with 21 L. Shoot/root ratio did not change with rooting volumes. Regardless of rooting volume, higher air temperatures on west-facing aspects led to afternoon leaf stress. In practice, for each cubic meter of rooting volume, 21 m2 (P. pandorana) and 10 m2 (A. quinata) canopy coverage can be expected within six months.

Effects of Intermittent Normoxia on Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Rats.

Liu, Chunlei, Xu Chen, Ge Guo, Xiang Xu, Xin Li, Qingxia Wei, Yanying Shen, Hanlu Li, Jianxiu Hao, Ya Ping Tian, and Kunlun He. Effects of intermittent normoxia on chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats. High Alt Med Biol. 22: 184-192, 2021. Background: Individuals with chronically low arterial oxygen tension owing to high altitude develop elevated rates of pulmonary hypertension (PH) and right ventricular (RV) hypertrophy. However, the effects of the frequency and duration of normoxic exposure on PH and RV hypertrophy have not been adequately assessed; thus, we aimed to analyze the same. Materials and Methods: PH and RV hypertrophy were induced in 60 rats using a hypobaric chamber. Of these 60 rats, every 10 were exposed to normoxic conditions for 30 minutes once (1T/D), three times (3T/D), or five times daily (5T/D), or for one 150-minute recovery daily (1LT/D). Furthermore, 10 rats were housed in a normoxic environment, and another 10 were subjected to continuous hypoxia. After 4 weeks, hemodynamic measurements were recorded, and the hearts were harvested for pathomorphological observations. Results: Average pulmonary arterial pressures (PAP) of control rats and those exposed to hypobaric hypoxia were 14.1 and 32.3 mmHg, respectively. After 30 minutes of exposure to normoxia 3T/D, 5T/D, or 1LT/D, PAP values were reduced to 27.1, 27.9, or 26.8 mmHg, respectively. Four weeks of hypoxic exposure elevated the RV/heart weight (HW) ratios, while exposure to normoxia 3T/D, 5T/D, and 1LT/D significantly reduced RV/HW. In addition, exposure to normoxia 3T/D, 5T/D, 1LT/D reduced the percentage wall thickness of the pulmonary artery as well as the hypertrophy indices of atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain 7 (MYH-7). Conclusions: Thirty-minute exposure to normoxic conditions of 3T/D, 5T/D, or 1LT/D effectively ameliorates PH and RV thickening.

Spectral cues and temporal integration during cylinder echo discrimination by bottlenose dolphins (Tursiops truncatus).

Three bottlenose dolphins (Tursiops truncatus) participated in simulated cylinder wall thickness discrimination tasks utilizing electronic "phantom" echoes. The first experiment resulted in psychometric functions (percent correct vs wall thickness difference) similar to those produced by a dolphin performing the task with physical cylinders. In the second experiment, a wide range of cylinder echoes was simulated, with the time separation between echo highlights covering a range from <30 to >300 μs. Dolphin performance and a model of the dolphin auditory periphery suggest that the dolphins used high-frequency, spectral-profiles of the echoes for discrimination and that the utility of spectral cues degraded when the time separation between echo highlights approached and exceeded the dolphin's temporal integration time of ∼264 μs.

Influence of MgO-Lignin Dual Component Additives on Selected Properties of Low Density Polyethylene.

The presented study describes the application of lignin-based dual component fillers into low-density polyethylene (LDPE) and an examination of their selected properties. The main experimental procedure was focused on the preparation of thin sheet films using polyethylene and its composites with 5% by wt. of fillers: MgO, MgO-lignin dual phase systems with varying amounts of lignin and pristine lignin. Analysis of morphology revealed that elongated voids appeared in the structure for hybrid filler with a higher content of lignin (min. 50% by wt. of lignin versus MgO) and also for pristine lignin. Moreover, the prepared sheets were subjected to the thermoforming process by using the positive forming method (male mold). The thermoforming ability of all composites was evaluated by means of a comparison of wall thickness distribution on thermoformed shapes. The most noticeable percentage of wall thinning occurred for films which consisted of LDPE/MgO-lignin (5:1 wt./wt.) composite. In contrast, the best material arrangement and the highest mean percentage wall thickness were observed in the case of the shape formed with LDPE/MgO-lignin (1:5 wt./wt.). In addition, as part of research studies, the measurements of the contact angle have been conducted. The analysed LDPE films, in particular LDPE/MgO-L, have been recognized as materials with high wettability.

Multislice computed tomography multiplanar reconstruction chest and three-dimensional reconstruction imaging of the airway remodeling in evaluation of asthma and chronic obstructive lung disease

Objective This study aims to estimate the role of multislice computed tomography multiplanar reconstruction and three dimensional in evaluation of the airway remodeling and lung parenchyma in patients with asthma and those with chronic obstructive lung disease. Patients and methods Asthmatic patients (n=19) and patients with chronic obstructive pulmonary disease (COPD) (n=31) underwent chest high-resolution computed tomography. We selected the apical bronchus (B1) and the posterior basal bronchus (B10) of the right lung. A segmental bronchus was defined as the third-generation bronchus. Wall area (WA) was calculated as Ao−Ai. The percentage wall area (WA%) was calculated as (WA/Ao)×100 and then assessed for each generation from two bronchi. Results Total WA% in patients ranged between 74.6 and 95.2, with a mean±SD of 84.9±5.5. Although the total WA% in patients with asthma was higher than in those with COPD (86.1±5.8 vs. 84.1±5.3), it was not statistically significant (P=0.231). Regarding the parenchymatous lung changes, these changes were detected in patients with both disease groups; Hounsfield unit ranged between −1042 and −855, with a mean±SD of −944.0±56.1. We demonstrated that COPD group had statistically significantly lower Hounsfield unit (mean±SD=−959.8±57.8) compared with bronchial asthma group (mean±SD=−919.1±34.1), with P=0.006. Conclusion Quantitative computed tomography has been widely used as an imaging tool in patients with COPD and those with bronchial asthma. Now it is possible to analyze the lung parenchyma and airways quantitatively using digital data from computed tomography.

Therapeutic Ultrasound Improves Myocardial Blood Flow and Reduces Infarct Size in a Canine Model of Coronary Microthromboembolism

Therapeutic ultrasound (TUS) has been used to lyse infarct-related coronary artery thrombus. There has been no study examining the effect of TUS specifically on myocardial microthromboemboli seen in acute myocardial infarction and acute coronary syndromes. The aim of this study was to test the hypothesis that TUS improves myocardial blood flow (MBF) and reduces infarct size (IS) in this situation by dissolving myocardial microthrombi. An open-chest canine model of myocardial microthromboembolism was created by disrupting a thrombus in the left anterior descending coronary artery, and 1.05- and 0.25-MHz TUS (n=7 each) delivered epicardially for 30min was compared with control (n=6). MBF and IS (as a percentage of left anterior descending coronary artery perfusion bed size) were measured 60min after treatment. In addition, immunohistochemistry was performed to assess microthrombi, and histopathology was performed to define inflammation. Transmural, epicardial, and endocardial myocardial blood volume and MBF (measured using myocardial contrast echocardiography) and percentage wall thickening were significantly higher 60min after receiving TUS compared with control. The ratio of IS to left anterior descending coronary artery perfusion bed size was significantly smaller (P=.03) in the 1.05-MHz TUS group (0.14±0.04) compared with the control (0.31±0.06, P=.04) and 0.25-MHz (0.36±0.08) groups. MBF versus percentage wall thickening exhibited a linear relation (r=0.65) in the control and 1.05-MHz TUS groups but not in the 0.25-MHz TUS group (r=0.29). The presence of myocardial microemboli in vessels >10μm in diameter was significantly reduced in the 1.05-MHz TUS group compared with the other two groups. The distribution and intensity of inflammation was higher in the 0.25-MHz TUS group compared with the other groups. TUS at 1.05MHz is effective in restoring myocardial blood volume and MBF, thus reducing IS by clearing the microcirculation of microthrombi. IS reduction is not seen at 0.25MHz, despite improvement in MBF, which may be related to the increased inflammation noted at this frequency. Because both acute myocardial infarction and acute coronary syndromes are associated with microthromboembolism, these results suggest that TUS could have a potential adjunctive role in the treatment of both conditions.

Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning.

Left ventricular hypertrophy (LVH) in aortic stenosis (AS) varies widely before and after aortic valve replacement (AVR), and deeper phenotyping beyond traditional global measures may improve risk stratification. We hypothesized that machine learning derived 3D LV models may provide a more sensitive assessment of remodelling and sex-related differences in AS than conventional measurements. One hundred and sixteen patients with severe, symptomatic AS (54% male, 70 ± 10 years) underwent cardiovascular magnetic resonance pre-AVR and 1 year post-AVR. Computational analysis produced co-registered 3D models of wall thickness, which were compared with 40 propensity-matched healthy controls. Preoperative regional wall thickness and post-operative percentage wall thickness regression were analysed, stratified by sex. AS hypertrophy and regression post-AVR was non-uniform-greatest in the septum with more pronounced changes in males than females (wall thickness regression: -13 ± 3.6 vs. -6 ± 1.9%, respectively, P < 0.05). Even patients without LVH (16% with normal indexed LV mass, 79% female) had greater septal and inferior wall thickness compared with controls (8.8 ± 1.6 vs. 6.6 ± 1.2 mm, P < 0.05), which regressed post-AVR. These differences were not detectable by global measures of remodelling. Changes to clinical parameters post-AVR were also greater in males: N-terminal pro-brain natriuretic peptide (NT-proBNP) [-37 (interquartile range -88 to -2) vs. -1 (-24 to 11) ng/L, P = 0.008], and systolic blood pressure (12.9 ± 23 vs. 2.1 ± 17 mmHg, P = 0.009), with changes in NT-proBNP correlating with percentage LV mass regression in males only (ß 0.32, P = 0.02). In patients with severe AS, including those without overt LVH, LV remodelling is most plastic in the septum, and greater in males, both pre-AVR and post-AVR. Three-dimensional machine learning is more sensitive than conventional analysis to these changes, potentially enhancing risk stratification. Regression of myocardial fibrosis after aortic valve replacement (RELIEF-AS); NCT02174471. https://clinicaltrials.gov/ct2/show/NCT02174471.

Effect of Sublingual Immunotherapy on Airway Inflammation and Airway Wall Thickness in Allergic Asthma

The efficacy of the standardized quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT) has been demonstrated for respiratory allergic disease. However, the effects of SLIT on inflammation and structural changes of the airways are still unknown. The aim of this study was to assess the effects of the 6 SQ-HDM SLIT on airway inflammation and airway geometry in allergic asthma and rhinitis. One hundred two asthmatic patients with rhinitis sensitized to HDM were randomized to receive either SLIT plus pharmacotherapy or standard pharmacotherapy alone, for 48 weeks. Fractional exhaled nitric oxide (FeNO), pulmonary function, quantitative computed tomography, and clinical symptoms were performed at baseline and end of the study. Compared with pharmacotherapy, SLIT demonstrated a significant reduction of FeNO (P < .01), airway wall area/body surface area (WA/BSA, P < .001), wall thickness (T/√BSA, P < .001), percentage wall area (WA/Ao, P < .01), increase in luminal area (Ai/BSA, P < .05), improvement of airflow limitation (P < .001), and clinical symptom scores (P<.05). The change in forced expiratory volume in 1 second (FEV1) was correlated with both changes in FeNO and airway dimensions. Multiple regression analysis showed that the change in FeNO was independently associated with an increase in FEV1 in the SLIT group (r2= 0.623, P= .037). Adding 6 SQ-HDM SLIT to standard asthma therapy provides a significant improvement in symptoms and pulmonary function compared with pharmacotherapy. Improvement of airflow limitation with SLIT was associated with the decrease in eosinophilic airway inflammation.

Multicenter Interrater Reliability in the Endoscopic Assessment of Velopharyngeal Function Using a Video Instruction Tool.

Assess interrater agreement of endoscopic assessment of velopharyngeal (VP) function before and after viewing the video instruction tool (VIT). We hypothesized improvement in interrater agreement using the Golding-Kushner scale (GKS) after viewing the VIT. Prospective study. Multi-institutional. Sixteen fellowship-trained pediatric otolaryngologists who treat velopharyngeal insufficiency (VPI) rated 50 video segments using the GKS before and after watching the VIT. Raters assessed gap size percentage and lateral pharyngeal wall (LPW), soft palate (SP), and posterior pharyngeal wall (PPW) movement. Intraclass correlation coefficient was estimated for these continuous measures. Raters also indicated the presence of a palatal notch, Passavant's ridge, and aberrant pulsations (categorical variables). Fleiss κ coefficient was used for categorical variables. Wilcoxon signed-rank test was performed on the difference between the pre/post individual video ratings. Reliability improved for all continuous variables after watching the instructional video. The improvement was significant for PPW (0.22-0.30, P < .001), SP (left: 0.63-0.68, P < .001 and right: 0.64-0.68, P = .001), and LPW (left: 0.49-0.54, P = .01 and right: 0.49-0.54, P = .09) but not significant for gap size (0.65-0.69, P = .36). Among categorical variables, agreement on Passavant's ridge significantly improved (0.30-0.36, P = .03). Exposure to a video instruction tool improves interrater agreement of endoscopic assessment of VP function. Significant improvement was observed in our primary end points, specifically posterior pharyngeal wall movement, soft palate movement, and lateral pharyngeal wall movement. There was less impact of the VIT on the interrater agreement of the categorical variables, palatal notch, Passavant's ridge, and aberrant pulsations.

Longitudinal airway remodeling in active and past smokers in a lung cancer screening population.

To longitudinally investigate smoking cessation-related changes of quantitative computed tomography (QCT)-based airway metrics in a group of heavy smokers. CT scans were acquired in a lung cancer screening population over 4years at 12-month intervals in 284 long-term ex-smokers (ES), 405 continuously active smokers (CS), and 31 subjects who quitted smoking within 2years after baseline CT (recent quitters, RQ). Total diameter (TD), lumen area (LA), and wall percentage (WP) of 1st-8th generation airways were computed using airway analysis software. Inter-group comparison was performed using Mann-Whitney U test or Student's t test (two groups), and ANOVA or ANOVA on ranks with Dunn's multiple comparison test (more than two groups), while Fisher's exact test or chi-squared test was used for categorical data. Multiple linear regression was used for multivariable analysis. At any time, TD and LA were significantly higher in ES than CS, for example, in 5th-8th generation airways at baseline with 6.24mm vs. 5.93mm (p < 0.001) and 15.23mm2 vs. 13.51mm2 (p < 0.001), respectively. RQ showed higher TD (6.15mm vs. 5.93mm, n.s.) and significantly higher LA (14.77mm2 vs. 13.51mm2, p < 0.001) than CS after 3years, and after 4years. In multivariate analyses, smoking status independently predicted TD, LA, and WP at baseline, at 3years and 4years (p < 0.01-0.001), with stronger impact than pack years. Bronchial dimensions depend on the smoking status. Smoking-induced airway remodeling can be partially reversible after smoking cessation even in long-term heavy smokers. Therefore, QCT-based airway metrics in clinical trials should consider the current smoking status besides pack years. • Airway lumen and diameter are decreased in active smokers compared to ex-smokers, and there is a trend towards increased airway wall thickness in active smokers. • Smoking-related airway changes improve within 2years after smoking cessation. • Smoking status is an independent predictor of airway dimensions.

Quantitative CT detects changes in airway dimensions and air-trapping after bronchial thermoplasty for severe asthma

ObjectivesBronchial thermoplasty (BT) can be considered in the treatment of severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We hypothesized that BT may thus have long-term effects on airway dimensions and air-trapping detectable by quantitative computed tomography (QCT). MethodsPaired in- and expiratory CT and inspiratory CT were acquired in 17 patients with severe asthma before and up to two years after bronchial thermoplasty and in 11 additional conservatively treated patients with serve asthma, respectively. A fully automatic software calculated the airways metrics for wall thickness (WT), wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung air-trapping was quantified by determining the quotient of mean lung attenuation in expiration vs. inspiration (E/I MLA) and relative volume change in the Hounsfield interval −950 to −856 in expiration to inspiration (RVC856-950) in a generation- and lobe-based approach, respectively. ResultsBT reduced WT for the combined analysis of the 2nd–7th airway generation significantly by 0.06 mm (p = 0.026) and WP by 2.05% (p < 0.001), whereas LA and TD did not change significantly (p = 0.147, p = 0.706). No significant changes were found in the control group. Furthermore, E/I MLA and RVC856-950 decreased significantly after BT by 12.65% and 1.77% (p < 0.001), respectively. ConclusionBT significantly reduced airway narrowing and air-trapping in patients with severe asthma. This can be interpreted as direct therapeutic effects caused by a reduction in airway-smooth muscle mass and changes in innervation. A reduction in air-trapping indicates an influence on more peripheral airways not directly treated by the BT procedure.