Background: The prevalence of childhood overweight and obesity in developed countries appears to be plateauing. The purpose of this study was to provide the most recent data on the prevalence and trends in overweight and obesity among Chinese children and adolescents from 2011 to 2015.Methods: We used data collected in the China Health and Nutrition Survey (CHNS) and China Nutritional Transition Cohort Study (CNTCS). We used two waves of the survey in 12 provinces conducted in 2011 (aged 7-18 years; n = 1458) and 2015 (aged 7-18 years; n = 1084) to perform a trend analysis. We used data collected in 15 provinces (aged 7-18 years; n = 1617) to estimate the prevalence of overweight and obesity among Chinese children and adolescents in 2015.Results: In 2015, based on the Working Group for Obesity in China (WGOC) criteria, the prevalence of overweight and obesity were 14.0% (95% CI, 11.6-16.3) and 10.5% (95% CI, 8.4-12.6) in boys, and 9.7% (95% CI, 7.7-11.8) and 7.1% (95% CI, 5.2-8.9) in girls, respectively. The increase in BMI z-scores from 2011 to 2015 was statistically significant among adolescents (p = 0.0083), but not among children. No significant changes were observed in prevalence of overweight and obesity between 2011 and 2015, excepting adolescents aged 12-18 years (p = 0.0086).Conclusions: Since 2011, overweight has remained stable, and obesity has stabilized in children, though not in adolescents. Although levels of childhood overweight and obesity in China are not high compared to other developed countries, they remain concerning enough that effective policies and interventions need to be sustained and intensified for lowering rates of childhood overweight and obesity.

Most previous studies on trends in the prevalence of obesity or abdominal obesity in Chinese adults were based on regional data and/or short time intervals, and recent trends are not available. We aimed to examine the secular trends in the prevalence of overweight, obesity, and abdominal obesity among Chinese adults at the national level from 1993 to 2015.A total of 70,242 Chinese adults aged 18-80 years were from the cross-sectional surveys conducted from 1993 to 2015. According to the World Health Organization criteria, overweight was defined as body mass index (BMI) ≥23.0 kg/m and <27.5 kg/m, and obesity was defined as BMI ≥27.5 kg/m. According to the International Diabetes Federation criteria, abdominal obesity was defined as waist circumference (WC) ≥90 cm for men and ≥80 cm for women. Mean values and prevalence of adiposity markers were standardized to the age distribution of the China population in 2010.Between 1993 and 2015, and based on age-standardized values, mean BMI increased from 21.9 kg/m in 1993 to 23.9 kg/m (+2.0 kg/m) in 2015 (P for trend < 0.001), and mean WC increased from 76.0 cm to 83.4 cm (+7.4 cm) (P for trend <0.001). From 1993 to 2015, the prevalence increased from 26.6% to 41.3% (+14.7%) for overweight, from 4.2% to 15.7% (+11.5%) for obesity, and from 20.2% to 46.9% (+26.7%) for abdominal obesity (all P for trends < 0.001). In multivariate linear regression analysis, time (calendar years), older age and urban regions were strongly and independently associated with BMI.The prevalence of overweight, obesity, and abdominal obesity increased markedly among Chinese adults during the past two decades. Weight control programs and public health measures to address the societal causes of obesity should be strengthened.

This study examined the effects of overweight/obesity on mortality and morbidity outcomes and the disparities, time trends, and projected future obesity health burden in China.Cohort studies that were conducted in China and published in English or Chinese between January 1, 1995, and July 31, 2021, were systematically searched. This study focused on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension, cardiovascular diseases, metabolic syndrome, cancers, and chronic kidney disease.A total of 31 cohorts and 50 cohort studies reporting on mortality (n = 20) and morbidities (n = 30) associated with obesity met study inclusion criteria. Overall, BMI was nonlinearly (U-shaped) associated with all-cause mortality and linearly associated with risks of T2DM, cardiovascular diseases, hypertension, cancer, metabolic syndrome, and chronic kidney disease. In 2018, among adults, the prevalence of overweight/obesity, hypertension, and T2DM was 51.2%, 27.5%, and 12.4%, respectively. Their future projected prevalence would be 70.5%, 35.4%, and 18.5% in 2030, respectively. The projected number of adults having these conditions would be 810.65 million, 416.47 million, and 217.64 million, respectively. The urban-rural disparity in overweight/obesity prevalence was projected to shrink and then reverse over time.The current health burden of obesity in China is high and it will sharply increase in coming years and affect population groups differently. China needs to implement vigorous interventions for obesity prevention and treatment.© 2022 The Obesity Society.

The relationship between body weight and lung function is complex. Using a dyadic multilevel linear modeling approach, treating body mass index (BMI; weight (kg)/height (m)2) and lung function as paired, within-person outcomes, we tested the hypothesis that persons with more rapid increase in BMI exhibit more rapid decline in lung function, as measured by forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio (FEV1:FVC). Models included random intercepts and slopes and adjusted for sociodemographic and smoking-related factors. A sample of 9,115 adults with paired measurements of BMI and lung function taken at ≥3 visits were selected from a pooled set of 5 US population-based cohort studies (1983-2018; mean age at baseline = 46 years; median follow-up, 19 years). At age 46 years, average annual rates of change in BMI, FEV1, FVC, and FEV1:FVC ratio were 0.22 kg/m2/year, -25.50 mL/year, -21.99 mL/year, and -0.24%/year, respectively. Persons with steeper BMI increases had faster declines in FEV1 (r = -0.16) and FVC (r = -0.26) and slower declines in FEV1:FVC ratio (r = 0.11) (all P values < 0.0001). Results were similar in subgroup analyses. Residual correlations were negative (P < 0.0001), suggesting additional interdependence between BMI and lung function. Results show that greater rates of weight gain are associated with greater rates of lung function loss.© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

To explore mechanisms of restrictive respiratory physiology and high pleural pressure (P(Pl)) in severe obesity, we studied 51 obese subjects (body mass index = 38-80.7 kg/m(2)) and 10 nonobese subjects, both groups without lung disease, anesthetized, and paralyzed for surgery. We measured esophageal and gastric pressures (P(Es), P(Ga)) using a balloon-catheter, airway pressure (P(AO)), flow, and volume. We compared P(Es) to another estimate of P(Pl) based on P(AO) and flow. Reasoning that the lungs would not inflate until P(AO) exceeded alveolar and pleural pressures (P(AO) > P(Alv) > P(Pl)), we disconnected subjects from the ventilator for 10-15 s to allow them to reach relaxation volume (V(Rel)) and then slowly raised P(AO) until lung volume increased by 10 ml, indicating the "threshold P(AO)" (P(AO-Thr)) for inflation, which we took to be an estimate of the lowest P(Alv) or P(Pl) to be found in the chest at V(Rel). P(AO-Thr) ranged from 0.6 to 14.0 cmH2O in obese and 0.2 to 0.9 cmH2O in control subjects. P(Es) at V(Rel) was higher in obese than control subjects (12.5 +/- 3.9 vs. 6.9 +/- 3.1 cmH2O, means +/- SD; P = 0.0002) and correlated with P(AO-Thr) (R(2) = 0.16, P = 0.0015). Respiratory system compliance (C(RS)) was lower in obese than control (0.032 +/- 0.008 vs. 0.053 +/- 0.007 l/cmH2O) due principally to lower lung compliance (0.043 +/- 0.016 vs. 0.084 +/- 0.029 l/cmH2O) rather than chest wall compliance (obese 0.195 +/- 0.109, control 0.223 +/- 0.132 l/cmH2O). We conclude that many severely obese supine subjects at relaxation volume have positive P(pl) throughout the chest. High P(Es) suggests high P(Pl) in such individuals. Lung and respiratory system compliances are low because of breathing at abnormally low lung volumes.

The worldwide prevalence of obesity has increased rapidly in the last 3 decades, and this increase has led to important changes in the pathogenesis and clinical presentation of many common diseases. This review article examines the relationship between obesity and lung disease, highlighting some of the major findings that have advanced our understanding of the mechanisms contributing to this relationship. Changes in pulmonary function related to fat mass are important, but obesity is much more than simply a state of mass loading, and BMI is only a very indirect measure of metabolic health. The obese state is associated with changes in the gut microbiome, cellular metabolism, lipid handling, immune function, insulin resistance, and circulating factors produced by adipose tissue. Together, these factors can fundamentally alter the pathogenesis and pathophysiology of lung health and disease.Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The role of obesity on dyspnea in chronic obstructive pulmonary disease (COPD) patients remains unclear. We aimed to provide an assessment of dyspnea in COPD patients according to their Body Mass Index (BMI) and to investigate the impact of obesity on dyspnea according to COPD severity.One hundred and twenty seven COPD patients with BMI ≥ 18.5 kg/m² (63% male, median (interquartile range) post bronchodilator forced expiratory volume of 1 second (post BD FEV) at 51 (34-66) % pred) were consecutively included. Dyspnea was assessed by mMRC (Modified medical research council) scale. Lung function tests were recorded, and emphysema was quantified on CT-scan (computed tomography-scan).Twenty-five percent of the patients were obese (BMI ≥ 30kg/m²), 66% of patients experienced disabling dyspnea (mMRC ≥ 2). mMRC scores did not differ depending on BMI categories (2 (1-3) for normal weight, 2 (1-3) 1 for overweight and 2 (1-3) for obese patients; p = 0.71). Increased mMRC scores (0-1 versus 2-3 versus 4) were associated with decreased post BD-FEV (p < 0.01), higher static lung hyperinflation (inspiratory capacity/total lung capacity (IC/TLC), p < 0.01), reduced DLCO (p < 0.01) and higher emphysema scores (p < 0.01). Obese patients had reduced static lung hyperinflation (IC/TLC p < 0.01) and lower emphysema scores (p < 0.01) than non-obese patients. mMRC score increased with GOLD grades (1-2 versus 3-4) in non-obese patients but not in obese patients, in association with a trend towards reduced static lung hyperinflation and lower emphysema scores.By contrast with non-obese patients, dyspnea did not increase with spirometric GOLD grades in obese patients. This might be explained by a reduced lung hyperinflation related to the mechanical effects of obesity and a less severe emphysema in severe COPD patients with obesity.© 2024 Dupuis et al.

Background: Pulmonary function tests (PFTs) are routinely performed in the upright position due to measurement devices and patient comfort. This systematic review investigated the influence of body position on lung function in healthy persons and specific patient groups.Methods: A search to identify English-language papers published from 1/1998-12/2017 was conducted using MEDLINE and Google Scholar with key words: body position, lung function, lung mechanics, lung volume, position change, positioning, posture, pulmonary function testing, sitting, standing, supine, ventilation, and ventilatory change. Studies that were quasi-experimental, pre-post intervention; compared >= 2 positions, including sitting or standing; and assessed lung function in non-mechanically ventilated subjects aged >= 18 years were included. Primary outcome measures were forced expiratory volume in 1s (FEV1), forced vital capacity (FVC, FEV1/FVC), vital capacity (VC), functional residual capacity (FRC), maximal expiratory pressure (PEmax), maximal inspiratory pressure (PImax), peak expiratory flow (PEF), total lung capacity (TLC), residual volume (RV), and diffusing capacity of the lungs for carbon monoxide (DLCO). Standing, sitting, supine, and right- and left-side lying positions were studied.Results: Forty-three studies met inclusion criteria. The study populations included healthy subjects (29 studies), lung disease (nine), heart disease (four), spinal cord injury (SCI, seven), neuromuscular diseases (three), and obesity (four). In most studies involving healthy subjects or patients with lung, heart, neuromuscular disease, or obesity, FEV1, FVC, FRC, PEmax, PImax, and/or PEF values were higher in more erect positions. For subjects with tetraplegic SCI, FVC and FEV1 were higher in supine vs. sitting. In healthy subjects, DLCO was higher in the supine vs. sitting, and in sitting vs. side-lying positions. In patients with chronic heart failure, the effect of position on DLCO varied.Conclusions: Body position influences the results of PFTs, but the optimal position and magnitude of the benefit varies between study populations. PFTs are routinely performed in the sitting position. We recommend the supine position should be considered in addition to sitting for PFTs in patients with SCI and neuromuscular disease. When treating patients with heart, lung, SCI, neuromuscular disease, or obesity, one should take into consideration that pulmonary physiology and function are influenced by body position.

Obesity is associated with important decrements in lung volumes. Despite this, ventilation remains normally or near normally distributed at least for moderate decrements in functional residual capacity (FRC). We tested the hypothesis that this is because maximum flow increases presumably as a result of an increased lung elastic recoil. Forced expiratory flows corrected for thoracic gas compression volume, lung volumes, and forced oscillation technique at 5-11-19 Hz were measured in 133 healthy subjects with a body mass index (BMI) ranging from 18 to 50 kg/m(2). Short-term temporal variability of ventilation heterogeneity was estimated from the interquartile range of the frequency distribution of the difference in inspiratory resistance between 5 and 19 Hz (R5-19_IQR). FRC % predicted negatively correlated with BMI (r = -0.72, P < 0.001) and with an increase in slope of either maximal (r = -0.34, P < 0.01) or partial flow-volume curves (r = -0.30, P < 0.01). Together with a slight decrease in residual volume, this suggests an increased lung elastic recoil. Regression analysis of R5-19_IQR against FRC % predicted and expiratory reserve volume (ERV) yielded significantly higher correlation coefficients by nonlinear than linear fitting models (r(2) = 0.40 vs. 0.30 for FRC % predicted and r(2) = 0.28 vs. 0.19 for ERV). In conclusion, temporal variability of ventilation heterogeneities increases in obesity only when FRC falls approximately below 65% of predicted or ERV below 0.6 liters. Above these thresholds distribution is quite well preserved presumably as a result of an increase in lung recoil.

: Obesity-associated asthma represents a heterogeneous group of clinical phenotypes, including an adult-onset phenotype. These patients often have difficult to control symptoms and often are less likely to respond to conventional asthma therapies.: This review covers the effects of lifestyle interventions, including diet and weight loss, effect asthma outcomes and how obesity-associated asthma responds to conventional approaches to asthma management.: Management of obesity-associated asthma should include lifestyle modifications aimed at weight reduction, management of other co-morbidities, and limiting systemic steroids. As many of these patients have non-Th2 asthma, long-acting muscarinic antagonists and macrolides may be potentially helpful. Medications to treat metabolic syndrome.

Obesity is associated with reduced operating lung volumes that may contribute to increased airway closure during tidal breathing and abnormalities in ventilation distribution. We investigated the effect of obesity on the topographical distribution of ventilation before and after methacholine-induced bronchoconstriction using single-photon emission computed tomography (SPECT)-computed tomography (CT) in healthy subjects. Subjects with obesity (= 9) and subjects without obesity (= 10) underwent baseline and postbronchoprovocation SPECT-CT imaging, in which Technegas was inhaled upright and followed by supine scanning. Lung regions that were nonventilated (Vent), low ventilated (Vent), or well ventilated (Vent) were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. To determine regional ventilation, lungs were divided into upper, middle, and lower thirds of axial length, derived from CT. At baseline, Vent and Vent for the entire lung were similar in subjects with and without obesity. However, in the upper lung zone, Vent (17.5 ± 10.6% vs. 34.7 ± 7.8%, < 0.001) and Vent (25.7 ± 6.3% vs. 33.6 ± 5.1%, < 0.05) were decreased in subjects with obesity, with a consequent increase in Vent (56.8 ± 9.2% vs. 31.7 ± 10.1%, < 0.001). The greater diversion of ventilation to the upper zone was correlated with body mass index ( = 0.74, < 0.001), respiratory system resistance ( = 0.72, < 0.001), and respiratory system reactance ( = -0.64, = 0.003) but not with lung volumes or basal airway closure. Following bronchoprovocation, overall Vent increased similarly in both groups; however, in subjects without obesity, Vent only increased in the lower zone, whereas in subjects with obesity, Vent increased more evenly across all lung zones. In conclusion, obesity is associated with altered ventilation distribution during baseline and following bronchoprovocation, independent of reduced lung volumes. Using ventilation SPECT-computed tomography imaging in healthy subjects, we demonstrate that ventilation in obesity is diverted to the upper lung zone and that this is strongly correlated with body mass index but is independent of operating lung volumes and of airway closure. Furthermore, methacholine-induced bronchoconstriction only occurred in the lower lung zone in individuals who were not obese, whereas in subjects who were obese, it occurred more evenly across all lung zones. These findings show that obesity-associated factors alter the topographical distribution of ventilation.

Obesity is a global and growing public health problem. Bariatric surgery (BS) is indicated in patients with morbid obesity. To our knowledge, the effects of morbid obesity and BS on ventilation/perfusion (V.a/Q.) ratio distributions using the multiple inert gas elimination technique have never before been explored.We compared respiratory and inert gas (V.a/Q. ratio distributions) pulmonary gas exchange, breathing both ambient air and 100% oxygen, in 19 morbidly obese women (BMI, 45 kg/m2), both before and 1 year after BS, and in eight normal-weight, never smoker, age-matched, healthy women.Before BS, morbidly obese individuals had reduced arterial Po2 (76 ± 2 mm Hg) and an increased alveolar-arterial Po2 difference (27 ± 2 mm Hg) caused by small amounts of shunt (4.3% ± 1.1% of cardiac output), along with abnormally broadly unimodal blood flow dispersion (0.83 ± 0.06). During 100% oxygen breathing, shunt increased twofold in parallel with a reduction of blood flow to low V.a/Q. units, suggesting the development of reabsorption atelectasis without reversion of hypoxic pulmonary vasoconstriction. After BS, body weight was reduced significantly (BMI, 31 kg/m2), and pulmonary gas exchange abnormalities were decreased.Morbid obesity is associated with mild to moderate shunt and V.a/Q. imbalance. These abnormalities are reduced after BS.

The effects of moderate weight loss on operational lung volumes during exercise and the oxygen (O2) cost of breathing are unknown in obese women but could have important implications regarding exercise endurance.In 29 obese women (33±8 years, 97±14 kg, body mass index: 36±4 kg m(-2), body fat: 45.6±4.5%; means±s.d.), body composition, fat distribution (by magnetic resonance imaging), pulmonary function, operational lung volumes during exercise and the O2 cost of breathing during eucapnic voluntary hyperpnea (([Vdot ]O2) vs ([Vdot ]E) slope) were studied before and after a 12-week diet and resistance exercise weight loss program.Participants lost 7.5±3.1 kg or ≈8% of body weight (P<0.001), but fat distribution remained unchanged. After weight loss, lung volume subdivisions at rest were increased (P<0.05) and were moderately associated (P<0.05) with changes in weight. End-expiratory lung volume (percentage of total lung capacity) increased at rest and during constant load exercise (P<0.05). O2 cost of breathing was reduced by 16% (2.52±1.02-2.11±0.72 ml l(-1); P=0.003). As a result, O2 uptake of the respiratory muscles ([Vdot ]O2Resp), estimated as the product of O2 cost of breathing and exercise ([Vdot ]E) during cycling at 60 W, was significantly reduced by 27±31 ml (P<0.001), accounting for 46% of the reduction in total body ([Vdot ]O2) during cycling at 60 W.Moderate weight loss yields important improvements in respiratory function at rest and during submaximal exercise in otherwise healthy obese women. These changes in breathing load could have positive effects on the exercise endurance and adherence to physical activity.

There is a major epidemic of obesity, and many obese patients suffer with respiratory symptoms and disease. The overall impact of obesity on lung function is multifactorial, related to mechanical and inflammatory aspects of obesity. Areas covered: Obesity causes substantial changes to the mechanics of the lungs and chest wall, and these mechanical changes cause asthma and asthma-like symptoms such as dyspnea, wheeze, and airway hyperresponsiveness. Excess adiposity is also associated with increased production of inflammatory cytokines and immune cells that may also lead to disease. This article reviews the literature addressing the relationship between obesity and lung function, and studies addressing how the mechanical and inflammatory effects of obesity might lead to changes in lung mechanics and pulmonary function in obese adults and children. Expert commentary: Obesity has significant effects on respiratory function, which contribute significantly to the burden of respiratory disease. These mechanical effects are not readily quantified with conventional pulmonary function testing and measurement of body mass index. Changes in mediators produced by adipose tissue likely also contribute to altered lung function, though as of yet this is poorly understood.

The growing epidemics of obesity and asthma are major public health concerns. Although asthma-obesity links are widely studied, the effects of weight loss on asthma severity measured by airway hyperresponsiveness (AHR) have received limited attention. The main study objective was to examine whether weight reduction reduces asthma severity in obese adults with asthma.In a prospective, controlled, parallel-group study, we followed 22 obese participants with asthma aged 18 to 75 years with a BMI ≥ 32.5 kg/m2 and AHR (provocative concentration of methacholine causing a 20% fall in FEV1 [PC20] < 16 mg/mL). Sixteen participants followed a behavioral weight reduction program for 3 months, and six served as control subjects. The primary outcome was change in AHR over 3 months. Changes in lung function, asthma control, and quality of life were secondary outcomes.At study entry, participant mean ± SD age was 44 ± 9 years, 95% were women, and mean BMI was 45.7 ± 9.2 kg/m2. After 3 months, mean weight loss was 16.5 ± 9.9 kg in the intervention group, and the control group had a mean weight gain of 0.6 ± 2.6 kg. There were significant improvements in PC20 (P =.009), FEV1 (P =.009), FVC (P =.010), asthma control (P <.001), and asthma quality of life (P =.003) in the intervention group, but these parameters remained unchanged in the control group. Physical activity levels also increased significantly in the intervention group but not in the control group.Weight loss in obese adults with asthma can improve asthma severity, AHR, asthma control, lung function, and quality of life. These findings support the need to actively pursue healthy weight-loss measures in this population.

Background There is significant pulmonary functional deficit related to obesity, but no prospective CT studies have evaluated the effects of obesity on the lungs and trachea. Purpose To evaluate lung parenchymal and tracheal CT morphology before and 6 months after bariatric surgery, with functional and symptomatic correlation. Materials and Methods A prospective longitudinal study of 51 consecutive individuals referred for bariatric surgery was performed (from November 2011 to November 2013). All individuals had undergone limited (three-location) inspiratory and end-expiratory thoracic CT before and after surgery, with concurrent pulmonary function testing, body mass index calculation, and modified Medical Research Council (mMRC) dyspnea scale and Epworth scoring. Two thoracic radiologists scored the CT extent of mosaic attenuation, end-expiratory air trapping, and tracheal shape. The inspiratory and end-expiratory cross-sectional areas of the trachea were measured. The paired test or Wilcoxon signed-rank test was used for pre- and postsurgical comparisons. Spearman correlation and logistic regression were used to evaluate correlations between CT findings and functional and symptom indexes. Results A total of 51 participants (mean age, 52 years ± 8 [standard deviation]; 20 men) were evaluated. Before surgery, air trapping extent correlated most strongly with decreased total lung capacity (Spearman rank correlation coefficient [] = -0.40, =.004). After surgery, there were decreases in percentage mosaic attenuation (0% [interquartile range {IQR}: 0%-2.5%] vs 0% [IQR: 0%-0%], <.001), air trapping (9.6% [IQR: 5.8%-15.8%] vs 2.5% [IQR: 0%-6.7%], <.001), and tracheal collapse (201 mm [IQR: 181-239 mm] vs 229 mm [186-284 mm], <.001). After surgery, mMRC dyspnea score change correlated positively with air trapping extent change (= 0.46, =.001) and end-expiratory tracheal shape change (= 0.40, =.01). At multivariable analysis, air trapping was the main determinant for decreased dyspnea after surgery (odds ratio, 1.2; 95% confidence interval: 1.1, 1.2; =.03). Conclusion Dyspnea improved in obese participants after weight reduction, which correlated with less tracheal collapse and air trapping at end-expiration chest CT. © RSNA, 2020

Chronic low-grade inflammation associated with obesity contributes to insulin resistance and type 2 diabetes. Helminth parasites are the strongest natural inducers of type 2 immune responses, and short-lived infection with rodent nematodes was reported to improve glucose tolerance in obese mice. Here, we investigated the effects of chronic infection (12 weeks) with Schistosoma mansoni, a helminth that infects millions of humans worldwide, on whole-body metabolic homeostasis and white adipose tissue (WAT) immune cell composition in high-fat diet-induced obese C57BL/6 male mice. Our data indicate that chronic helminth infection reduced body weight gain (-62%), fat mass gain (-89%), and adipocyte size; lowered whole-body insulin resistance (-23%) and glucose intolerance (-16%); and improved peripheral glucose uptake (+25%) and WAT insulin sensitivity. Analysis of immune cell composition by flow cytometry and quantitative PCR (qPCR) revealed that S. mansoni promoted strong increases in WAT eosinophils and alternatively activated (M2) macrophages. Importantly, injections with S. mansoni-soluble egg antigens (SEA) recapitulated the beneficial effect of parasite infection on whole-body metabolic homeostasis and induced type 2 immune responses in WAT and liver. Taken together, we provide novel data suggesting that chronic helminth infection and helminth-derived molecules protect against metabolic disorders by promoting a T helper 2 (Th2) response, eosinophilia, and WAT M2 polarization.© FASEB.

Eosinophils are associated with helminth immunity and allergy, often in conjunction with alternatively activated macrophages (AAMs). Adipose tissue AAMs are necessary to maintain glucose homeostasis and are induced by the cytokine interleukin-4 (IL-4). Here, we show that eosinophils are the major IL-4-expressing cells in white adipose tissues of mice, and, in their absence, AAMs are greatly attenuated. Eosinophils migrate into adipose tissue by an integrin-dependent process and reconstitute AAMs through an IL-4- or IL-13-dependent process. Mice fed a high-fat diet develop increased body fat, impaired glucose tolerance, and insulin resistance in the absence of eosinophils, and helminth-induced adipose tissue eosinophilia enhances glucose tolerance. Our results suggest that eosinophils play an unexpected role in metabolic homeostasis through maintenance of adipose AAMs.

Eosinophils in visceral adipose tissue (VAT) have been implicated in metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence of eosinophils can lead to adiposity and systemic insulin resistance in experimental animals, but what maintains eosinophils in adipose tissue is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation and results in increased adiposity and insulin resistance when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) are resident in VAT and are the major source of IL-5 and IL-13, which promote the accumulation of eosinophils and AAM. Deletion of ILC2s causes significant reductions in VAT eosinophils and AAMs, and also impairs the expansion of VAT eosinophils after infection with Nippostrongylus brasiliensis, an intestinal parasite associated with increased adipose ILC2 cytokine production and enhanced insulin sensitivity. Further, IL-33, a cytokine previously shown to promote cytokine production by ILC2s, leads to rapid ILC2-dependent increases in VAT eosinophils and AAMs. Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation.

Obesity is associated with chronic inflammation of the adipose tissue, which contributes to obesity-associated complications such as insulin resistance and type 2 diabetes. Interleukin (IL)-33 acts via its receptor ST2 and is involved in the pathogenesis of inflammatory disorders including atherosclerosis and heart disease. IL-33 has been demonstrated to promote endothelial cell inflammatory response, but also anti-inflammatory and protective actions such as TH2 and M2 polarization of T cells and macrophages, respectively. IL-33 and ST2 have been shown to be expressed in human and murine adipose tissue. Our objective was to investigate alterations in obesity and a possible role of IL-33 in adipose tissue inflammation.We investigated severely obese patients (BMI>40 kg m(-2), n=20) and lean to overweight controls (BMI<30 kg m(-2); n=20) matched for age and sex, as well as diet-induced obese and db/db mice, in order to determine the impact of obesity on IL-33 and ST2 gene and protein expression levels in adipose tissue and blood, and their correlation with inflammatory and metabolic parameters. Furthermore, we examined the cellular source and location of IL-33 and ST2 in situ.IL-33 and ST2 expression levels were markedly elevated in omental and subcutaneous adipose tissue of severely obese humans and in diet-induced obese mice, but not in leptin receptor-deficient db/db mice. In addition, soluble ST2, but not IL-33 serum levels, were elevated in obesity. The main source for IL-33 in adipose tissue were endothelial cells, which, in humans, exclusively expressed ST2 on their surface. IL-33 expression strongly correlated with leptin expression in human adipose tissue.Expression of IL-33 and its receptor ST2 in human adipose tissue is predominantly detectable in endothelial cells and increased by severe obesity indicating an autocrine action. Thus, the adipose tissue microvasculature could participate in obesity-associated inflammation and related complications via IL-33/ST2.

Foxp3(+)  CD4(+) regulatory T (Treg) cells, recognized to be one of the most important defences of the human body against an inappropriate immune response, have recently gained attention from those outside immunology thanks to the compelling evidence for their capability to exert non-canonical immune functions in a variety of tissues in health and disease. The recent discovery of the differences between tissue-resident Treg cells and those derived from lymphoid organs is affecting the mindset of many investigators now questioning the broad applicability of observations originally based on peripheral blood/lymphoid organ cells. So far, the best characterized 'Treg flavour' comes from studies focused on their role in suppressing adipose tissue inflammation and obesity-driven insulin resistance. Adipose tissue derived Treg cells are distinct from their counterparts in lymphoid organs based on their transcriptional profile, T-cell receptor repertoire, and cytokine and chemokine receptor expression pattern. These cells are abundant in visceral adipose tissue of lean mice but their number is greatly reduced in insulin-resistant animal models of obesity. Interestingly, peroxisome-proliferator-activated receptor γ expression by visceral adipose tissue Treg cells is crucial for their accumulation, phenotype and function in the fat and surprisingly necessary for complete restoration of insulin sensitivity in obese mice by the anti-diabetic drug Pioglitazone. This review surveys recent findings relating to the unique phenotype and function of adipose tissue-resident Treg cells, speculates on the nature of their dynamics in lean and obese mouse models, and analyses their potential therapeutic application in the treatment of type 2 diabetes. © 2014 John Wiley & Sons Ltd.

Chronic, low-grade adipose tissue inflammation is a key etiological mechanism linking the increasing incidence of type 2 diabetes (T2D) and obesity. It is well recognized that the immune system and metabolism are highly integrated, and macrophages, in particular, have been identified as critical effector cells in the initiation of inflammation and insulin resistance. Recent advances have been made in the understanding of macrophage recruitment and retention to adipose tissue and the participation of other immune cell populations in the regulation of this inflammatory process. Here we discuss the pathophysiological link between macrophages, obesity, and insulin resistance, highlighting the dynamic immune cell regulation of adipose tissue inflammation. We also describe the mechanisms by which inflammation causes insulin resistance and the new therapeutic targets that have emerged. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic, low-grade inflammation of visceral adipose tissue, and systemically, is a critical link between recent strikingly parallel rises in the incidence of obesity and type 2 diabetes. Macrophages have been recognized for some time to be critical participants in obesity-induced inflammation of adipose tissue. Of late, a score of other cell types of the innate and adaptive arms of the immune system have been suggested to play a positive or negative role in adipose tissue infiltrates. This piece reviews the existing data on these new participants; discusses experimental uncertainties, inconsistencies, and complexities; and puts forward a minimalist synthetic scheme.Copyright © 2013 Elsevier Inc. All rights reserved.

Recent years have seen several advances in our understanding of the functions of adipose tissue regarding not only the energy storage, but also the regulation of complex metabolic and endocrine functions. In this context, leptin and adiponectin, the two most abundant adipocyte products, represent one of the best example of adipocytokines involved in the control of energy expenditure, lipid and carbohydrate metabolism as well as in the regulation of immune responses. Leptin and adiponectin secretion is counter-regulated in vivo, in relation to degree of adiposity, since plasma leptin concentrations are significantly elevated in obese subjects in proportion to body mass index while adiponectin secretion decreases in relation to the amount of adipose tissue. In this review we focus on the main biological activities of leptin and adiponectin on the lipid and carbohydrate metabolism and on their contribute in regulation of innate and adaptive immune responses.Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.

The presence of T lymphocytes in human adipose tissue has only recently been demonstrated and relatively little is known of their potential relevance in the development of obesity-related diseases. We aimed to further characterise these cells and in particular to investigate how they interact with modestly increased levels of adiposity typical of common overweight and obesity.Subcutaneous adipose tissue and fasting blood samples were obtained from healthy males aged 35-55 years with waist circumferences in lean (<94 cm), overweight (94-102 cm) and obese (>102 cm) categories. Adipose tissue-resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by gene expression and flow cytometry. T lymphocytes were further characterised by their expression of activation markers CD25 and CD69. Adipose tissue inflammation was investigated using gene expression analysis and tissue culture.Participants reflected a range of adiposity from lean to class I obesity. Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA transcripts, was elevated in subcutaneous adipose tissue with increased levels of adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed significant correlations between waist circumference and levels of CD25 and CD69 expression per cell on activated adipose tissue-resident CD4+ and CD8+ T lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were found with blood T lymphocytes. This increased T lymphocyte activation was related to increased expression and secretion of various pro- and anti-inflammatory cytokines from subcutaneous whole adipose tissue explants.This is the first study to demonstrate that even modest levels of overweight/obesity elicit modifications in adipose tissue immune function. Our results underscore the importance of T lymphocytes during adipose tissue expansion, and the presence of potential compensatory mechanisms that may work to counteract adipose tissue inflammation, possibly through an increased number of T-regulatory cells.

Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction has a primary importance in obesity. Large amounts of macrophages are accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway also promotes more macrophage accumulation into the obese adipose tissue. However, increased local extracellular lipid concentrations is a final mechanism for adipose tissue macrophage accumulation. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-alpha) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1beta) by macrophages; both adipocyte and macrophage induction by toll like receptor-4 (TLR4) through nuclear factor-kappaB (NF-kappaB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in macrophage accumulation and in the development of adipose tissue inflammation. Old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. The obesity-induced changes in adipose tissue macrophage numbers are mainly due to increases in the triple-positive CD11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. The ratio of M1-to-M2 macrophages is increased in obesity. Furthermore, hypoxia along with higher concentrations of free fatty acids exacerbates macrophage-mediated inflammation in obesity. The metabolic status of adipocytes is a major determinant of macrophage inflammatory output. Macrophage/adipocyte fatty-acid-binding proteins act at the interface of metabolic and inflammatory pathways. Both macrophages and adipocytes are the sites for active lipid metabolism and signaling.

The pathogenesis of asthma in obese subjects is poorly understood and has been described as a specific phenotype in these patients. Weight loss improves asthma control and lung function. Whether this improvement is the result of better mechanical properties of the airways or decreased systemic and bronchial inflammation remains unclear.A longitudinal study in obese patients with asthma (bariatric surgery and asthma group (BS+A), n=27) and obese control (bariatric surgery without asthma group (BS-A), n=39) subjects undergoing bariatric surgery, and obese patients with asthma without intervention (no bariatric surgery and asthma group (NBS+A), n=12). Lung function, asthma control, cellular infiltrates in bronchial biopsies and circulating markers of systemic inflammation were measured during follow up at 3, 6 and 12 months.Bariatric surgery resulted in a profound weight loss at 12 months. In the BS+A group as well as the BS-A group FEV1, functional residual capacity, total lung capacity improved, whereas FEV1/FVC only improved in the BS-A group. In addition, Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire, inhaled corticosteroid use and PD20 improved in BS+A, whereas in the NBS+A group only ACQ improved. Small airway function R5-R20 improved in both surgery groups, however the change in the BS+A group was greater, resulting in a comparable R5-R20 between BS+A and BS-A at 12-month follow-up. Besides improvement of systemic inflammation (high sensitivity C-reactive protein, adiponectin and leptin) after BS, only a decrease in mast cell numbers was detectable in the BS+A group.Bariatric surgery improved small airway function, decreased systemic inflammation and number of mast cells in the airways. These effects could explain the improvement of asthma control, quality of life and lung function. Therefore bariatric surgery, in addition to all other positive effects, also improves asthma in subjects with morbid obesity.3204.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Guidelines for management of chronic obstructive pulmonary disease (COPD) primarily focus on the prevention of weight loss, while overweight and obesity are highly prevalent in patients with milder stages of COPD. This cross-sectional study examines the association of overweight and obesity with the prevalence of comorbid disorders and prescribed medication for obstructive airway disease, in patients with mild to moderate COPD. Data were used from electronic health records of 380 Dutch general practices in 2014. In total, we identified 4938 patients with mild or moderate COPD based on spirometry data, and a recorded body mass index (BMI) of >= 21 kg/m(2). Outcomes in overweight (BMI >= 25 and < 30 kg/m(2)) and obese (BMI >= 30 kg/m(2)) patients with COPD were compared to those with a normal weight (BMI >= 21 and < 25 kg/m(2)), by logistic multilevel analyses. Compared to COPD patients with a normal weight, positive associations were found for diabetes, osteoarthritis, and hypertension, for both overweight (OR: 1.4-1.7) and obese (OR: 2.4-3.8) patients, and for heart failure in obese patients (OR: 2.3). Osteoporosis was less prevalent in overweight (OR: 0.7) and obese (OR: 0.5) patients, and anxiety disorders in obese patients (OR: 0.5). No associations were found for coronary heart disease, stroke, sleep disturbance, depression, and pneumonia. Furthermore, obese patients were in general more often prescribed medication for obstructive airway disease compared to patients with a normal weight. The findings of this study underline the need to increase awareness in general practitioners for excess weight in patients with mild to moderate COPD.

Obesity is a major risk factor for asthma; the reasons for this are poorly understood, although it is thought that inflammatory changes in adipose tissue in obesity could contribute to airway inflammation and airway reactivity in individuals who are obese.To determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity.We recruited a cohort of obese women with asthma and obese control women. We followed subjects with asthma for 12 months after bariatric surgery. We compared markers in adipose tissue and the airway from subjects with asthma and control subjects, and changes in subjects with asthma over time.Subjects with asthma had increased macrophage infiltration of visceral adipose tissue (P < 0.01), with increased expression of leptin (P < 0.01) and decreased adiponectin (p < 0.001) when controlled for body mass index. Similar trends were observed in subcutaneous adipose tissue. Airway epithelial cells expressed receptors for leptin and adiponectin, and airway reactivity was significantly related to visceral fat leptin expression (rho = -0.8; P < 0.01). Bronchoalveolar lavage cytokines and cytokine production from alveolar macrophages were similar in subjects with asthma and control subjects at baseline, and tended to increase 12 months after surgery.Obesity is associated with increased markers of inflammation in serum and adipose tissue, and yet decreased airway inflammation in obese people with asthma; these patterns reverse with bariatric surgery. Leptin and other adipokines may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing airway inflammation.

Allergic asthma is a common respiratory disease that significantly impacts human health. Through in silico analysis of human lung RNASeq, we found that asthmatic lungs display lower levels of Isthmin-1 (ISM1) expression than healthy lungs. ISM1 is an endogenous anti-inflammatory protein that is highly expressed in mouse lungs and bronchial epithelial cells, playing a crucial role in maintaining lung homeostasis. However, how ISM1 influences asthma remains unclear. This study aims to investigate the potential involvement of ISM1 in allergic airway inflammation and uncover the underlying mechanisms.We investigated the pivotal role of ISM1 in airway inflammation using an ISM1 knockout mouse line (ISM1) and challenged them with house dust mite (HDM) extract to induce allergic-like airway/lung inflammation. To examine the impact of ISM1 deficiency, we analyzed the infiltration of immune cells into the lungs and cytokine levels in bronchoalveolar lavage fluid (BALF) using flow cytometry and multiplex ELISA, respectively. Furthermore, we examined the therapeutic potential of ISM1 by administering recombinant ISM1 (rISM1) via the intratracheal route to rescue the effects of ISM1 reduction in HDM-challenged mice. RNA-Seq, western blot, and fluorescence microscopy techniques were subsequently used to elucidate the underlying mechanisms.ISM1 mice showed a pronounced worsening of allergic airway inflammation and hyperresponsiveness upon HDM challenge. The heightened inflammation in ISM1 mice correlated with enhanced lung cell necroptosis, as indicated by higher pMLKL expression. Intratracheal delivery of rISM1 significantly reduced the number of eosinophils in BALF and goblet cell hyperplasia. Mechanistically, ISM1 stimulates adiponectin secretion by type 2 alveolar epithelial cells partially through the GRP78 receptor and enhances adiponectin-facilitated apoptotic cell clearance via alveolar macrophage efferocytosis. Reduced adiponectin expression under ISM1 deficiency also contributed to intensified necroptosis, prolonged inflammation, and heightened severity of airway hyperresponsiveness.This study revealed for the first time that ISM1 functions to restrain airway hyperresponsiveness to HDM-triggered allergic-like airway/lung inflammation in mice, consistent with its persistent downregulation in human asthma. Direct administration of rISM1 into the airway alleviates airway inflammation and promotes immune cell clearance, likely by stimulating airway adiponectin production. These findings suggest that ISM1 has therapeutic potential for allergic asthma.© 2023. The Author(s).

The present study aimed to assess the effects of therapy with adiponectin (APN) gene-modified adipose-derived stem cells (ADSCs) on pulmonary arterial hypertension (PAH) in rats and the underlying cellular and molecular mechanisms. ADSCs were successfully isolated from the rats and characterized. ADSCs were effectively infected with the green fluorescent protein (GFP)-empty (ADSCs-V) or the APN-GFP (ADSCs-APN) lentivirus and the APN expression was evaluated by ELISA. Sprague-Dawley rats were administered monocrotaline (MCT) to develop PAH. The rats were treated with MCT, ADSCs, ADSCs-V and ADSCs-APN. Then ADSCs-APN in the lung were investigated by confocal laser scanning microscopy and western blot analysis. Engrafted ADSCs in the lung were located around the vessels. Mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RVHI) in the ADSCs-APN-treated mice were significantly decreased as compared with the ADSCs and ADSCs-V treatments. Pulmonary vascular remodeling was assessed. Right ventricular (RV) function was evaluated by echocardiography. We found that pulmonary vascular remodeling and the parameters of RV function were extensively improved after ADSCs-APN treatment when compared with ADSCs and ADSCs-V treatment. Pulmonary artery smooth muscle cells (PASMCs) were isolated from the PAH rats. The antiproliferative effect of APN on PASMCs was assayed by Cell Counting Kit-8. The influence of APN and specific inhibitors on the levels of bone morphogenetic protein (BMP), adenosine monophosphate activated protein kinase (AMPK), and small mothers against decapentaplegia (Smad) pathways was detected by western blot analysis. We found that APN suppressed the proliferation of PASMCs isolated from the PAH rats by regulating the AMPK/BMP/Smad pathway. This effect was weakened by addition of the AMPK inhibitor (compound C) and BMP2 inhibitor (noggin). Therefore, combination treatment with ADSCs and APN effectively attenuated PAH in rats by inhibiting PASMC proliferation and regulating the AMPK/BMP/Smad pathway.

The current obesity epidemic poses a major public health issue since obesity predisposes towards several chronic diseases. BMI and total adiposity are positively correlated with cardiometabolic disease risk at the population level. However, body fat distribution and an impaired adipose tissue function, rather than total fat mass, better predict insulin resistance and related complications at the individual level. Adipose tissue dysfunction is determined by an impaired adipose tissue expandability, adipocyte hypertrophy, altered lipid metabolism, and local inflammation. Recent human studies suggest that adipose tissue oxygenation may be a key factor herein. A subgroup of obese individuals - the 'metabolically healthy obese' (MHO) - have a better adipose tissue function, less ectopic fat storage, and are more insulin sensitive than obese metabolically unhealthy persons, emphasizing the central role of adipose tissue function in metabolic health. However, controversy has surrounded the idea that metabolically healthy obesity may be considered really healthy since MHO individuals are at increased (cardio)metabolic disease risk and may have a lower quality of life than normal weight subjects due to other comorbidities. Detailed metabolic phenotyping of obese persons will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed to identify high-risk individuals or subgroups, thereby paving the way for optimization of prevention and treatment strategies to combat cardiometabolic diseases.© 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

As one of the critical indicators of obesity, the interaction between visceral fat content and lung disease is the focus of current research. However, the exact relationship between Visceral adipose index (VAI) and lung function is not fully understood. The purpose of this study was to evaluate the relationship between VAI and lung function, METHODS: Our study included all participants from the baseline survey population in Xinjiang in the Natural Population Cohort Study in Northwest China. A field survey was conducted in rural areas of Moyu County, Xinjiang, China, between 35 and 74 years old from June to December 2018. We collected standard questionnaires and completed physical examinations, visceral fat tests, and lung function measurements.The study included 2367 participants with a mean VAI of 10.35 ± 4.35, with males having a significantly higher VAI than females: 13.17 ± 3.91 vs. 7.58 ± 2.65. The piecewise linear spline models indicated a significant threshold effect between lung function and VAI in the general population and the males population, showing an inverted U-shaped curve. But there was no significant association between VAI and lung function in females. FEV1% predicted and FVC% predicted increased with the increase of VAI (β 0.76; 95% CI 0.30, 1.21) and (β 0.50; 95% CI 0.06, 0.94) in males with VAI ≤ 14, while FEV1% predicted and FVC% predicted decreased with the increase of VAI (β - 1.17; 95% CI - 1.90, - 0.45) and (β - 1.36; 95% CI - 2.08, - 0.64) in males with VAI ≥ 15.The relationship between lung function and VAI in male participants showed an inverted U-shaped curve, with the turning point of VAI between 14 and 15. The association between visceral fat and lung function was more robust in males than in females.

Background: In adults, overweight is associated with reduced lung function, in children evidence on this association is conflicting. We examined the association of body mass index (BMI) and waist circumference (WC) at age 12, and of persistently (at ages 8 and 12 years) high BMI and large WC, with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at age 12. Methods: Height, weight, WC and FVC and FEV1 were measured during a medical examination in 1288 12-year-olds participating in the PIAMA birth cohort study. 1090 children also had BMI and WC measured at age 8. The associations between BMI and WC and FVC, FEV1, and FEV1/FVC ratio were studied using local and linear regression analyses, separately for girls and boys. The regression models were adjusted for age, height, and pubertal development and maternal educational level. Results: High BMI and large WC (sd-score >90th percentile) were associated with higher FVC; in girls these associations were statistically significant (4.6% (95% CI: 1.5, 7.9) and 3.6% (95% CI: 0.6, 6.8) respectively in adjusted models). Similar associations were observed for persistently high BMI or large WC: girls with a high BMI or large WC at both 8 and 12 years had statistically significantly higher FVC at age 12 years (BMI: 4.9% (95% CI 0.9, 9.1), WC: 5.0% (95% CI 0.7, 9.6)) than girls with normal BMI or WC at both ages. No statistically significant associations were observed between (persistently) high BMI or large WC and FEV1. The FEV1/FVC ratio was statistically significantly lower in children with a high BMI or large WC than in children with a normal BMI or WC. Girls and boys with a persistently high BMI or large WC status had statistically significantly lower FEV1/FVC ratios. Conclusion: At 12 years of age, a persistently high BMI or large WC is not yet associated with lower FVC and FEV1, suggesting that this association, that is commonly observed in adults, develops at a later age.

Preoperative chemoradiation has become a routine modality in the treatment of rectal carcinoma that may impair a patients general condition. In these patients, it is important to identify factors that influence postoperative recovery. Visceral obesity(VO) as a metabolic risk factor was studied in rectal cancer patients receiving preoperative chemoradiation.The impact of VO on post-operative outcome in rectal carcinoma surgery after preoperative chemoradiation was studied. In addition, the effect of chemoradiation on body composition was studied.The visceral fat area(VFA), total fat area(TFA) and skeletal muscle area(SMA) were measured on cross-sectional CT-slides in 74 patients who underwent rectal cancer surgery after chemoradiation. CT-scans taken before and after chemoradiation were analysed. Associations between VFA, per- and postoperative complications were studied. A VFA of 100 cm(2) and 130 cm(2) was used to differentiate between non-VO and VO.Using a VO cut-off point of a VFA of 100 cm(2), the VO patients had more per-operative blood loss(471 mL vs 271 mL p = 0.020), a higher complication rate(10% vs 49% p = 0.001), more ileus(2% vs 28% p = 0.027) and a longer length of stay(9.7days vs 13days p = 0.027). When a VFA of 130 cm(2) was used, VO patients showed more complications(17% vs 55%, p = 0.001) and ileus(10% vs 32% p = 0.017). During chemoradiation the SMA increased(Mean difference: 2.2 cm(2) p = 0.024), while the VFA showed no change.It appears that VO is associated with co-morbidity and poor outcome in rectal cancer patients. Using different cutoff values for VO different associations with outcome were found. SMA increased during chemoradiation, a phenomenon that remains to be explained.Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Visceral obesity (VO) is a risk factor for developing postoperative complications in patients undergoing abdominal oncological surgery. However, in ovarian cancer patients this influence of body composition on postoperative morbidity is not well established. The aim of this study is to assess the association between body composition and complications in patients with advanced ovarian cancer undergoing cytoreductive surgery.Patients with FIGO stage 3 or 4 ovarian cancer between 2006 and 2017 were included. Visceral fat area, total skeletal mass and total fat area were measured on a single slice on the level of L3-L4 of the preoperative CT-scan. VO was defined as visceral fat ≥100cm. The perioperative data were extracted retrospectively. A multivariate logistic regression analysis was performed to test the predictive value of multiple variables such as body composition, albumin levels and preoperative morbidity.298 consecutive patients out of nine referring hospitals were included. VO patients were more likely to be hypertensive (38% vs 17% p < 0.001), and to have an ASA 3 score (21% vs 10% P = 0.012). Complications occurred more often in VO patients (43% vs 21% P < 0.001). Thrombotic events were found in 4.9% of VO patients versus 0.6% of the non-visceral obese patients (p = 0.019). VO(OR: 4.37, p < 0.001), hypertension (OR:1.9, p = 0.046) and duration of surgery (OR: 1.004, p = 0.017) were predictors of post-surgical complications. Muscle mass is not a predictor of complications.Visceral obesity is associated with a higher occurrence of complications in patients with advanced ovarian cancer undergoing cytoreductive surgery.Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Although an inverse relationship between abdominal adiposity and pulmonary function has been suggested, direct measurement of abdominal adipose tissue has rarely been attempted. Our object is to determine the impact of abdominal adiposity on pulmonary function by directly measuring abdominal adipose tissue with abdominal computed tomography (CT). In this cross-sectional study, we included never-smokers between the ages of 18 and 85 yr, who had undergone spirometry and abdominal adipose tissue analysis with CT scans during November 1, 2005 to October 31, 2009 as part of the comprehensive health examination. Among a total of 3,469 participants, 890 (25.7%) were male. The mean body mass index and waist circumference among males and females were 24.6 kg/m(2) and 87.8 cm and 23.0 kg/m(2) and 83.0 cm, respectively. Although total adipose tissue (TAT) of the abdomen in males (269.1 cm(2)) was similar to that in females (273.6 cm(2)), the ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) was different; 0.99 in males and 0.50 in females. In males, TAT, SAT, and VAT were inversely associated with the absolute value of forced vital capacity (FVC), and TAT and VAT were inversely associated with forced expiratory volume in one second (FEV(1)). However, in females, TAT and VAT, but not SAT, were inversely associated with absolute FVC and FEV(1) values. In conclusion, the amount of abdominal adipose tissue directly measured using CT is inversely associated with lung function.

To develop a reliable and reproducible automatic technique to segment and measure SAT and VAT based on MRI.Chemical-shift water-fat MRI were taken on twelve obese adolescents (mean age: 16.1±0.6, BMI: 31.3±2.3) recruited under the health monitoring program. The segmentation applied a spoke template created using Midpoint Circle algorithm followed by Bresenham's Line algorithm to detect narrow connecting regions between subcutaneous and visceral adipose tissues. Upon satisfaction of given constrains, a cut was performed to separate SAT and VAT. Bone marrow was consisted in pelvis and femur. By using the intensity difference in T2*, a mask was created to extract bone marrow adipose tissue (MAT) from VAT. Validation was performed using a semi-automatic method. Pearson coefficient, Bland-Altman plot and intra-class coefficient (ICC) were applied to measure accuracy and reproducibility.Pearson coefficient indicated that results from the proposed method achieved high correlation with the semi-automatic method. Bland-Altman plot and ICC showed good agreement between the two methods. Lowest ICC was obtained in VAT segmentation at lower regions of the abdomen while the rests were all above 0.80. ICC (0.98-0.99) also indicated the proposed method performed good reproducibility.No user interaction was required during execution of the algorithm and the segmented images and volume results were given as output. This technique utilized the feature in the regions connecting subcutaneous and visceral fat and T2* intensity difference in bone marrow to achieve volumetric measurement of various types of adipose tissue in abdominal site.Copyright © 2017. Published by Elsevier Inc.

To evaluate and compare conventional T1-weighted 2D turbo spin echo (TSE), T1-weighted 3D volumetric interpolated breath-hold examination (VIBE), and two-point 3D Dixon-VIBE sequences for automatic segmentation of visceral adipose tissue (VAT) volume at 3 Tesla by measuring and compensating for errors arising from intensity nonuniformity (INU) and partial volume effects (PVE).The body trunks of 28 volunteers with body mass index values ranging from 18 to 41.2 kg/m (30.02 ± 6.63 kg/m) were scanned at 3 Tesla using three imaging techniques. Automatic methods were applied to reduce INU and PVE and to segment VAT. The automatically segmented VAT volumes obtained from all acquisitions were then statistically and objectively evaluated against the manually segmented (reference) VAT volumes.Comparing the reference volumes with the VAT volumes automatically segmented over the uncorrected images showed that INU led to an average relative volume difference of -59.22 ± 11.59, 2.21 ± 47.04, and -43.05 ± 5.01 % for the TSE, VIBE, and Dixon images, respectively, while PVE led to average differences of -34.85 ± 19.85, -15.13 ± 11.04, and -33.79 ± 20.38 %. After signal correction, differences of -2.72 ± 6.60, 34.02 ± 36.99, and -2.23 ± 7.58 % were obtained between the reference and the automatically segmented volumes. A paired-sample two-tailed t test revealed no significant difference between the reference and automatically segmented VAT volumes of the corrected TSE (p = 0.614) and Dixon (p = 0.969) images, but showed a significant VAT overestimation using the corrected VIBE images.Under similar imaging conditions and spatial resolution, automatically segmented VAT volumes obtained from the corrected TSE and Dixon images agreed with each other and with the reference volumes. These results demonstrate the efficacy of the signal correction methods and the similar accuracy of TSE and Dixon imaging for automatic volumetry of VAT at 3 Tesla.

To validate a fully automated adipose segmentation method with magnetic resonance imaging (MRI) fat fraction abdominal imaging. We hypothesized that this method is suitable for segmentation of subcutaneous adipose tissue (SAT) and intra-abdominal adipose tissue (IAAT) in a wide population range, easy to use, works with a variety of hardware setups, and is highly repeatable.Analysis was performed comparing precision and analysis time of manual and automated segmentation of single-slice imaging, and volumetric imaging (78-88 slices). Volumetric and single-slice data were acquired in a variety of cohorts (body mass index [BMI] 15.6-41.76) including healthy adult volunteers, adolescent volunteers, and subjects with nonalcoholic fatty liver disease and lipodystrophies. A subset of healthy volunteers was analyzed for repeatability in the measurements.The fully automated segmentation was found to have excellent agreement with manual segmentation with no substantial bias across all study cohorts. Repeatability tests showed a mean coefficient of variation of 1.2 ± 0.6% for SAT, and 2.7 ± 2.2% for IAAT. Analysis with automated segmentation was rapid, requiring 2 seconds per slice compared with 8 minutes per slice with manual segmentation.We demonstrate the ability to accurately and rapidly segment regional adipose tissue using fat fraction maps across a wide population range, with varying hardware setups and acquisition methods.© 2014 Wiley Periodicals, Inc.

Pretreatment risk stratification is key for personalized medicine. While many physicians rely on an "eyeball test" to assess whether patients will tolerate major surgery or chemotherapy, "eyeballing" is inherently subjective and difficult to quantify. The concept of morphometric age derived from cross-sectional imaging has been found to correlate well with outcomes such as length of stay, morbidity, and mortality. However, the determination of the morphometric age is time intensive and requires highly trained experts. In this study, we propose a fully automated deep learning system for the segmentation of skeletal muscle cross-sectional area (CSA) on an axial computed tomography image taken at the third lumbar vertebra. We utilized a fully automated deep segmentation model derived from an extended implementation of a fully convolutional network with weight initialization of an ImageNet pre-trained model, followed by post processing to eliminate intramuscular fat for a more accurate analysis. This experiment was conducted by varying window level (WL), window width (WW), and bit resolutions in order to better understand the effects of the parameters on the model performance. Our best model, fine-tuned on 250 training images and ground truth labels, achieves 0.93 ± 0.02 Dice similarity coefficient (DSC) and 3.68 ± 2.29% difference between predicted and ground truth muscle CSA on 150 held-out test cases. Ultimately, the fully automated segmentation system can be embedded into the clinical environment to accelerate the quantification of muscle and expanded to volume analysis of 3D datasets.

We aimed to develop and validate a deep learning system for fully automated segmentation of abdominal muscle and fat areas on computed tomography (CT) images.A fully convolutional network-based segmentation system was developed using a training dataset of 883 CT scans from 467 subjects. Axial CT images obtained at the inferior endplate level of the 3rd lumbar vertebra were used for the analysis. Manually drawn segmentation maps of the skeletal muscle, visceral fat, and subcutaneous fat were created to serve as ground truth data. The performance of the fully convolutional network-based segmentation system was evaluated using the Dice similarity coefficient and cross-sectional area error, for both a separate internal validation dataset (426 CT scans from 308 subjects) and an external validation dataset (171 CT scans from 171 subjects from two outside hospitals).The mean Dice similarity coefficients for muscle, subcutaneous fat, and visceral fat were high for both the internal (0.96, 0.97, and 0.97, respectively) and external (0.97, 0.97, and 0.97, respectively) validation datasets, while the mean cross-sectional area errors for muscle, subcutaneous fat, and visceral fat were low for both internal (2.1%, 3.8%, and 1.8%, respectively) and external (2.7%, 4.6%, and 2.3%, respectively) validation datasets.The fully convolutional network-based segmentation system exhibited high performance and accuracy in the automatic segmentation of abdominal muscle and fat on CT images.Copyright © 2020 The Korean Society of Radiology.

Body composition analysis (BCA) generates objective anthropometric data that can inform prognostication and treatment decisions across a wide variety of urologic conditions. A patient's body composition, specifically muscle and adipose tissue mass, may be characterized via segmentation of cross-sectional images (computed tomography, magnetic resonance imaging) obtained as part of routine clinical care. Unfortunately, conventional semi-automated segmentation techniques are time- and resource-intensive, precluding translation into clinical practice. Machine learning (ML) offers the potential to automate and scale rapid and accurate BCA. To date, ML for BCA has relied on algorithms called convolutional neural networks designed to detect and analyze images in ways similar to human neuronal connections. This mini review provides a clinically oriented overview of ML and its use in BCA. We address current limitations and future directions for translating ML and BCA into clinical practice. PATIENT SUMMARY: Body composition analysis is the measurement of muscle and fat in your body based on analysis of computed tomography or magnetic resonance imaging scans. We discuss the use of machine learning to automate body composition analysis. The information provided can be used to guide shared decision-making and to help in identifying the best therapy option.Copyright © 2021. Published by Elsevier B.V.

: Specification of adipose tissues by whole-body magnetic resonance imaging (MRI) was performed and related to pulmonary function parameters in a population-based cohort. : 203 study participants underwent whole-body MRI and pulmonary function tests as part of the KORA (Cooperative Health Research in the Augsburg Region) MRI study. Both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were derived from the T1-Dixon sequence, and hepatic adipose tissue from the proton density fat fraction (PDFF). Associations between adipose tissue parameters and spirometric indices such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and Tiffeneau-index (FEV1/FVC) were examined using multivariate linear regression analysis excluding cofounding effects of other clinical parameters. : VAT (β = -0.13, = 0.03) and SAT (β = -0.26, < 0.001), but not PDFF were inversely associated with FEV1, while VAT (β = -0.27, < 0.001), SAT (β = -0.41, < 0.001), and PDFF (β = -0.17, = 0.002) were inversely associated with FVC. PDFF was directly associated with the Tiffeneau index (β = 2.46, < 0.001). : In the adjusted linear regression model, VAT was inversely associated with all measured spirometric parameters, while PDFF revealed the strongest association with the Tiffeneau index. Non-invasive adipose tissue quantification measurements might serve as novel biomarkers for respiratory impairment.

Decreased airway lumen size and increased lung volume are major structural changes in chronic obstructive pulmonary disease (COPD). However, even though the outer wall of the airways is connected with lung parenchyma and the mechanical properties of the parenchyma affect the behaviour of the airways, little is known about the interactions between airway and lung sizes on lung function and symptoms. The present study examined these effects by establishing a novel computed tomography (CT) index, namely, airway volume percent (AWV%), which was defined as a percentage ratio of the airway tree to lung volume.Inspiratory chest CT, pulmonary function, and COPD Assessment Tests (CAT) were analysed in 147 stable males with COPD. The whole airway tree was automatically segmented, and the percentage ratio of the airway tree volume in the right upper and middle-lower lobes to right lung volume was calculated as the AWV% for right lung. Low attenuation volume % (LAV%), total airway count (TAC), luminal area (Ai), and wall area percent (WA%) were also measured.AWV% decreased as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grade increased (p < 0.0001). AWV% was lower in symptomatic (CAT score ≥ 10) subjects than in non-symptomatic subjects (p = 0.036). AWV% was more closely correlated with forced expiratory volume in 1 s (FEV) and ratio of residual volume to total lung capacity (RV/TLC) than Ai, Ai to lung volume ratio, and volume of either the lung or the airway tree. Multivariate analyses showed that lower AWV% was associated with lower FEV and higher RV/TLC, independent of LAV%, WA%, and TAC.A disproportionally small airway tree with a relatively large lung could lead to airflow obstruction and gas trapping in COPD. AWV% is an easily measured CT biomarker that may elucidate the clinical impacts of the airway-lung interaction in COPD.

Over the past 100 years, many procedures have been developed for correcting restrictive thoracic deformities which cause thoracic insufficiency syndrome. However, none of them have been assessed by a robust metric incorporating thoracic dynamics. In this paper, we investigate the relationship between radiographic spinal curve and lung volumes derived from thoracic dynamic magnetic resonance imaging (dMRI). Our central hypothesis is that different anteroposterior major spinal curve types induce different restrictions on the left and right lungs and their dynamics.Retrospectively, we included 25 consecutive patients with thoracic insufficiency syndrome (14 neuromuscular, 7 congenital, 4 other) who underwent vertical expandable prosthetic titanium rib surgery and received preimplantation and postimplantation thoracic dMRI for clinical care. We measured thoracic and lumbar major curves by the Cobb measurement method from anteroposterior radiographs and classified the curves as per Scoliosis Research Society (SRS)-defined curve types. From 4D dMRI images, we derived static volumes and tidal volumes of left and right lung, along with left and right chest wall and left and right diaphragm tidal volumes (excursions), and analyzed their association with curve type and major curve angles.Thoracic and lumbar major curve angles ranged from 0 to 136 and 0 to 116 degrees, respectively. A dramatic postoperative increase in chest wall and diaphragmatic excursion was seen qualitatively. All components of volume increased postoperatively by up to 533%, with a mean of 70%. As the major curve, main thoracic curve (MTC) was associated with higher tidal volumes (effect size range: 0.7 to 1.0) than thoracolumbar curve (TLC) in preoperative and postoperative situation. Neither MTC nor TLC showed any meaningful correlation between volumes and major curve angles preoperatively or postoperatively. Moderate correlations (0.65) were observed for specific conditions like volumes at end-inspiration or end-expiration.The relationships between component tidal volumes and the spinal curve type are complex and are beyond intuitive reasoning and guessing. TLC has a much greater influence on restricting chest wall and diaphragm tidal volumes than MTC. Major curve angles are not indicative of passive resting volumes or tidal volumes.Level II-diagnostic.

Background Available methods to quantify regional dynamic thoracic function in thoracic insufficiency syndrome (TIS) are limited. Purpose To evaluate the use of quantitative dynamic MRI to depict changes in regional dynamic thoracic function before and after surgical correction of TIS. Materials and Methods Images from free-breathing dynamic MRI in pediatric patients with TIS (July 2009-August 2015) were retrospectively evaluated before and after surgical correction by using vertical expandable prosthetic titanium rib (VEPTR). Eleven volumetric parameters were derived from lung, chest wall, and diaphragm segmentations, and parameter changes before versus after operation were correlated with changes in clinical parameters. Paired analysis from Student test on MRI parameters and clinical parameters was performed to detect if changes (from preoperative to postoperative condition) were statistically significant. Results Left and right lung volumes at end inspiration and end expiration increased substantially after operation in pediatric patients with thoracic insufficiency syndrome, especially right lung volume with 22.9% and 26.3% volume increase at end expiration (=.001) and end inspiration (=.002), respectively. The average lung tidal volumes increased after operation for TIS; there was a 43.8% and 55.3% increase for left lung tidal volume and right lung tidal volume (<.001 for both), respectively. However, clinical parameters did not show significant changes from pre- to posttreatment states. Thoracic and lumbar Cobb angle were poor predictors of MRI tidal volumes (chest wall, diaphragm, and left and right separately), but assisted ventilation rating and forced vital capacity showed moderate correlations with tidal volumes (chest wall, diaphragm, and left and right separately). Conclusion Vertical expandable prosthetic titanium rib operation was associated with postoperative increases in all components of tidal volume (left and right chest wall and diaphragm, and left and right lung tidal volumes) measured at MRI. Clinical parameters did not demonstrate improvements in postoperative tidal volumes. © RSNA, 2019 See also the editorial by Paltiel in this issue.

Dynamic or 4D imaging of the thorax has many applications. Both prospective and retrospective respiratory gating and tracking techniques have been developed for 4D imaging via CT and MRI. For pediatric imaging, due to radiation concerns, MRI becomes the de facto modality of choice. In thoracic insufficiency syndrome (TIS), patients often suffer from extreme malformations of the chest wall, diaphragm, and/or spine with inability of the thorax to support normal respiration or lung growth (Campbell et al., 2003, Campbell and Smith, 2007), as such patient cooperation needed by some of the gating and tracking techniques are difficult to realize without causing patient discomfort and interference with the breathing mechanism itself. Therefore (ventilator-supported) free-breathing MRI acquisition is currently the best choice for imaging these patients. This, however, raises a question of how to create a consistent 4D image from such acquisitions. This paper presents a novel graph-based technique for compiling the best 4D image volume representing the thorax over one respiratory cycle from slice images acquired during unencumbered natural tidal-breathing of pediatric TIS patients.In our approach, for each coronal (or sagittal) slice position, images are acquired at a rate of about 200-300ms/slice over several natural breathing cycles which yields over 2000 slices. A weighted graph is formed where each acquired slice constitutes a node and the weight of the arc between two nodes defines the degree of contiguity in space and time of the two slices. For each respiratory phase, an optimal 3D spatial image is constructed by finding the best path in the graph in the spatial direction. The set of all such 3D images for a given respiratory cycle constitutes a 4D image. Subsequently, the best 4D image among all such constructed images is found over all imaged respiratory cycles. Two types of evaluation studies are carried out to understand the behavior of this algorithm and in comparison to a method called Random Stacking - a 4D phantom study and 10 4D MRI acquisitions from TIS patients and normal subjects. The 4D phantom was constructed by 3D printing the pleural spaces of an adult thorax, which were segmented in a breath-held MRI acquisition.Qualitative visual inspection via cine display of the slices in space and time and in 3D rendered form showed smooth variation for all data sets constructed by the proposed method. Quantitative evaluation was carried out to measure spatial and temporal contiguity of the slices via segmented pleural spaces. The optimal method showed smooth variation of the pleural space as compared to Random Stacking whose behavior was erratic. The volumes of the pleural spaces at the respiratory phase corresponding to end inspiration and end expiration were compared to volumes obtained from breath-hold acquisitions at roughly the same phase. The mean difference was found to be roughly 3%.The proposed method is purely image-based and post-hoc and does not need breath holding or external surrogates or instruments to record respiratory motion or tidal volume. This is important and practically warranted for pediatric patients. The constructed 4D images portray spatial and temporal smoothness that should be expected in a consistent 4D volume. We believe that the method can be routinely used for thoracic 4D imaging.Copyright © 2016 Elsevier B.V. All rights reserved.

Respiratory motion is a challenging factor for image acquisition and image-guided procedures in the abdominal and thoracic region. In order to address the issues arising from respiratory motion, it is often necessary to detect the respiratory signal. In this article, we propose a novel, purely image-based retrospective respiratory gating method for ultrasound and MRI. Further, we apply this technique to acquire breathing-affected 4D ultrasound with a wobbler probe and, similarly, to create 4D MR with a slice stacking approach. We achieve the gating with Laplacian eigenmaps, a manifold learning technique, to determine the low-dimensional manifold embedded in the high-dimensional image space. Since Laplacian eigenmaps assign to each image frame a coordinate in low-dimensional space by respecting the neighborhood relationship, they are well suited for analyzing the breathing cycle. We perform the image-based gating on several 2D and 3D ultrasound datasets over time, and quantify its very good performance by comparing it to measurements from an external gating system. For MRI, we perform the manifold learning on several datasets for various orientations and positions. We achieve very high correlations by a comparison to an alternative gating with diaphragm tracking.Copyright © 2011 Elsevier B.V. All rights reserved.

Four-dimensional computed tomography (4D-CT) has been widely used in radiation therapy to assess patient-specific breathing motion for determining individual safety margins. However, it has two major drawbacks: low soft-tissue contrast and an excessive imaging dose to the patient. This research aimed to develop a clinically feasible four-dimensional magnetic resonance imaging (4D-MRI) technique to overcome these limitations.The proposed 4D-MRI technique was achieved by continuously acquiring axial images throughout the breathing cycle using fast 2D cine-MR imaging, and then retrospectively sorting the images by respiratory phase. The key component of the technique was the use of body area (BA) of the axial MR images as an internal respiratory surrogate to extract the breathing signal. The validation of the BA surrogate was performed using 4D-CT images of 12 cancer patients by comparing the respiratory phases determined using the BA method to those determined clinically using the Real-time position management (RPM) system. The feasibility of the 4D-MRI technique was tested on a dynamic motion phantom, the 4D extended Cardiac Torso (XCAT) digital phantom, and two healthy human subjects.Respiratory phases determined from the BA matched closely to those determined from the RPM: mean (± SD) difference in phase: -3.9% (± 6.4%); mean (± SD) absolute difference in phase: 10.40% (± 3.3%); mean (± SD) correlation coefficient: 0.93 (± 0.04). In the motion phantom study, 4D-MRI clearly showed the sinusoidal motion of the phantom; image artifacts observed were minimal to none. Motion trajectories measured from 4D-MRI and 2D cine-MRI (used as a reference) matched excellently: the mean (± SD) absolute difference in motion amplitude: -0.3 (± 0.5) mm. In the 4D-XCAT phantom study, the simulated "4D-MRI" images showed good consistency with the original 4D-XCAT phantom images. The motion trajectory of the hypothesized "tumor" matched excellently between the two, with a mean (± SD) absolute difference in motion amplitude of 0.5 (± 0.4) mm. 4D-MRI was able to reveal the respiratory motion of internal organs in both human subjects; superior-inferior (SI) maximum motion of the left kidney of Subject #1 and the diaphragm of Subject #2 measured from 4D-MRI was 0.88 and 1.32 cm, respectively.Preliminary results of our study demonstrated the feasibility of a novel retrospective 4D-MRI technique that uses body area as a respiratory surrogate.

A retrospective, respiratory-gated technique for measuring dynamic changes in the upper airway over the respiratory cycle was developed, with the ultimate goal of constructing anatomically and functionally accurate upper airway models in obstructive sleep apnea patients.Three-dimensional cine, retrospective respiratory-gated, gradient echo imaging was performed in six adolescents being evaluated for polycystic ovary syndrome, a disorder with a high obstructive sleep apnea prevalence. A novel retrospective gating scheme, synchronized to flow from a nasal cannula, limited image acquisition to predefined physiological ranges. Images were evaluated with respect to contrast, airway signal leakage, and demonstration of dynamic airway area changes.Two patients were diagnosed with obstructive sleep apnea. Motion artifacts were absent in all image sets. Scan efficiency ranged from 48 to 88%. Soft tissue-to-airway contrast-to-noise ratio varied from 6.1 to 9.6. Airway signal leakage varied between 10 and 17% of soft tissue signal. Automated segmentation allowed calculation of airway area changes over the respiratory cycle. In one severe apnea patient, the technique allowed demonstration of asynchronous airway expansion and contraction above and below a severe constriction.Retrospective, respiratory gated imaging of the upper airway has been demonstrated, utilizing a gating algorithm to ensure acquisition over specified ranges of respiratory rate and tidal volume.Copyright © 2013 Wiley Periodicals, Inc.

A database of normative quantitative measures of regional thoracic ventilatory dynamics, which is essential to understanding better thoracic growth and function in children, does not exist.How to quantify changes in the components of ventilatory pump dynamics during childhood via thoracic quantitative dynamic MRI (QdMRI)?Volumetric parameters were derived via 51 dynamic MRI scans for left and right lungs, hemidiaphragms, and hemichest walls during tidal breathing. Volume-based symmetry and functional coefficients were defined to compare left and right sides and to compare contributions of the hemidiaphragms and hemichest walls with tidal volumes (TVs). Statistical analyses were performed to compare volume components among four age-based groups.Right thoracic components were significantly larger than left thoracic components, with average ratios of 1.56 (95% CI, 1.41-1.70) for lung TV, 1.81 (95% CI, 1.60-2.03) for hemidiaphragm excursion TV, and 1.34 (95% CI, 1.21-1.47) for hemichest wall excursion TV. Right and left lung volumes at end-expiration showed, respectively, a 44% and 48% increase from group 2 (8 ≤ age < 10) to group 3 (10 ≤ age < 12). These numbers from group 3 to group 4 (12 ≤ age ≤ 14) were 24% and 28%, respectively. Right and left hemichest wall TVs exhibited, respectively, 48% and 45% increases from group 3 to group 4.Normal right and left ventilatory volume components have considerable asymmetry in morphologic features and dynamics and change with age. Chest wall and diaphragm contributions vary in a likewise manner. Thoracic QdMRI can provide quantitative data to characterize the regional function and growth of the thorax as it relates to ventilation.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown to be a promising technique for assessing lung lesions. However, DCE-MRI often suffers from motion artifacts and insufficient imaging speed. Therefore, highly accelerated free-breathing DCE-MRI is of clinical interest for lung exams.To test the performance of rapid free-breathing DCE-MRI for simultaneous qualitative and quantitative assessment of pulmonary lesions using Golden-angle RAdial Sparse Parallel (GRASP) imaging.Prospective.Twenty-six patients (17 males, mean age = 55.1 ± 14.4) with known pulmonary lesions.3T MR scanner; a prototype fat-saturated, T -weighted stack-of-stars golden-angle radial sequence for data acquisition and a Cartesian breath-hold volumetric-interpolated examination (BH-VIBE) sequence for comparison.After a dual-mode GRASP reconstruction, one with 3-second temporal resolution (3s-GRASP) and the other with 15-second temporal resolution (15s-GRASP), all GRASP and BH-VIBE images were pooled together for blind assessment by two experienced radiologists, who independently scored the overall image quality, lesion delineation, overall artifact level, and diagnostic confidence of each case. Perfusion analysis was performed for the 3s-GRASP images using a Tofts model to generate the volume transfer coefficient (K) and interstitial volume (V).Nonparametric paired two-tailed Wilcoxon signed-rank test; Cohen's kappa; unpaired Student's t-test.15s-GRASP achieved comparable image quality with conventional BH-VIBE (P > 0.05), except for the higher overall artifact level in the precontrast phase (P = 0.018). The K and V in inflammation were higher than those in malignant lesions (K : 0.78 ± 0.52 min vs. 0.37 ± 0.22 min, P = 0.020; V : 0.36 ± 0.16 vs. 0.26 ± 0.1, P = 0.177). Also, the K and V in malignant lesions were also higher than those in benign lesions (K : 0.37 ± 0.22 min vs. 0.04 ± 0.04 min, P = 0.001; V : 0.26 ± 0.12 vs. 0.10 ± 0.00, P = 0.063).This feasibility study demonstrated the performance of high spatiotemporal resolution free-breathing DCE-MRI of the lung using GRASP for qualitative and quantitative assessment of pulmonary lesions.2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:459-468.© 2018 International Society for Magnetic Resonance in Medicine.

This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas--and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children.© 2015 Wiley Periodicals, Inc.

Lung perfusion assessment is critical for diagnosing and monitoring a variety of respiratory conditions. MRI perfusion provides a radiation-free technique, making it an ideal choice for longitudinal imaging in younger populations. This review focuses on the techniques and applications of MRI perfusion, including contrast-enhanced (CE) MRI and non-CE methods such as arterial spin labeling (ASL), fourier decomposition (FD), and hyperpolarized 129-Xenon (129-Xe) MRI. ASL leverages endogenous water protons as tracers for a non-invasive measure of lung perfusion, while FD offers simultaneous measurements of lung perfusion and ventilation, enabling the generation of ventilation/perfusion mapsHyperpolarized 129-Xe MRI emerges as a novel tool for assessing regional gas exchange in the lungs. Despite the promise of MRI perfusion techniques, challenges persist, including competition with other imaging techniques and the need for additional validation and standardization. In conditions such as cystic fibrosis and lung cancer, MRI has displayed encouraging results, whereas in diseases like chronic obstructive pulmonary disease, further validation remains necessary. In conclusion, while MRI perfusion techniques hold immense potential for a comprehensive, non-invasive assessment of lung function and perfusion, their broader clinical adoption hinges on technological advancements, collaborative research, and rigorous validation.Copyright © 2023 Elsevier Inc. All rights reserved.

To quantitatively evaluate lung perfusion using Fourier decomposition perfusion MRI. The Fourier decomposition (FD) method is a noninvasive method for assessing ventilation- and perfusion-related information in the lungs, where the perfusion maps in particular have shown promise for clinical use. However, the perfusion maps are nonquantitative and dimensionless, making follow-ups and direct comparisons between patients difficult. We present an approach to obtain physically meaningful and quantifiable perfusion maps using the FD method.The standard FD perfusion images are quantified by comparing the partially blood-filled pixels in the lung parenchyma with the fully blood-filled pixels in the aorta. The percentage of blood in a pixel is then combined with the temporal information, yielding quantitative blood flow values. The values of 10 healthy volunteers are compared with SEEPAGE measurements which have shown high consistency with dynamic contrast enhanced-MRI.All pulmonary blood flow (PBF) values are within the expected range. The two methods are in good agreement (mean difference = 0.2 mL/min/100 mL, mean absolute difference = 11 mL/min/100 mL, mean PBF-FD = 150 mL/min/100 mL, mean PBF-SEEPAGE = 151 mL/min/100 mL). The Bland-Altman plot shows a good spread of values, indicating no systematic bias between the methods.Quantitative lung perfusion can be obtained using the Fourier Decomposition method combined with a small amount of postprocessing.Copyright © 2013 Wiley Periodicals, Inc.

To compare unenhanced lung ventilation-weighted (VW) and perfusion-weighted (QW) imaging based on Fourier decomposition (FD) magnetic resonance (MR) imaging with the clinical reference standard single photon emission computed tomography (SPECT)/computed tomography (CT) in an animal experiment.The study was approved by the local animal care committee. Lung ventilation and perfusion was assessed in seven anesthetized pigs by using a 1.5-T MR imager and SPECT/CT. For time-resolved FD MR imaging, sets of lung images were acquired by using an untriggered two-dimensional balanced steady-state free precession sequence (repetition time, 1.9 msec; echo time, 0.8 msec; acquisition time per image, 118 msec; acquisition rate, 3.33 images per second; flip angle, 75°; section thickness, 12 mm; matrix, 128 × 128). Breathing displacement was corrected with nonrigid image registration. Parenchymal signal intensity was analyzed pixelwise with FD to separate periodic changes of proton density induced by respiration and periodic changes of blood flow. Spectral lines representing respiratory and cardiac frequencies were integrated to calculate VW and QW images. Ventilation and perfusion SPECT was performed after inhalation of dispersed technetium 99m ((99m)Tc) and injection of (99m)Tc-labeled macroaggregated albumin. FD MR imaging and SPECT data were independently analyzed by two physicians in consensus. A regional statistical analysis of homogeneity and pathologic signal changes was performed.Images acquired in healthy animals by using FD MR imaging and SPECT showed a homogeneous distribution of VW and QW imaging and pulmonary ventilation and perfusion, respectively. The gravitation-dependent signal distribution of ventilation and perfusion in all animals was similarly observed at FD MR imaging and SPECT. Incidental ventilation and perfusion defects were identically visualized by using both modalities.This animal experiment demonstrated qualitative agreement in the assessment of regional lung ventilation and perfusion between contrast media-free and radiation-free FD MR imaging and conventional SPECT/CT.© RSNA, 2011.

Ventilation-weighted Fourier decomposition-MRI (FD-MRI) has matured as a reliable technique for quantitative measures of regional lung ventilation in recent years, but has yet not been validated in COPD patients.To compare regional fractional lung ventilation obtained by ventilation-weighted FD-MRI with dynamic fluorinated gas washout MRI (F-MRI) and lung function test parameters.Prospective study.Twenty-seven patients with chronic obstructive pulmonary disease (COPD, median age 61 [54-67] years) were included.For FD-MRI and for F-MRI a spoiled gradient echo sequence was used at 1.5T.FD-MRI coronal slices were acquired in free breathing. Dynamic F-MRI was performed after inhalation of 25-30 L of a mixture of 79% fluorinated gas (C F) and 21% oxygen via a closed face mask tubing using a dedicated coil tuned to 59.9 MHz. F washout times in numbers of breaths (F-n) as well as fractional ventilation maps for both methods (FD-FV, F-FV) were calculated. Slices were matched using a landmark driven algorithm, and only corresponding slices with an overlap of >90% were coregistered for evaluation.The obtained parameters were correlated with each other using Spearman's correlation coefficient (r).FD-FV strongly correlated with F-n on a global (r = -0.72, P < 0.0001) as well as on a lobar level and with lung function test parameters (FD-FV vs. FEV1, r = 0.76, P < 0.0001). There was a small systematic overestimation of FD-FV compared to F-FV (mean difference -0.03 (95% confidence interval [CI]: -0.097; -0.045).Regional ventilation-weighted Fourier decomposition-MRI is a promising noninvasive, radiation-free tool for quantification of regional ventilation in COPD patients.2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1534-1541.© 2017 International Society for Magnetic Resonance in Medicine.

Free-breathing phase-resolved functional lung (PREFUL)-MRI may be useful for treatment monitoring in chronic obstructive pulmonary disease (COPD) patients with dyspnea. PREFUL test-retest reliability is essential for clinical application.To measure the repeatability of PREFUL-MRI ventilation (V) and perfusion (Q) parameters.Retrospective and prospective.A total of 28 COPD patients and 57 healthy subjects.1.5T MRI/2D spoiled gradient echo imaging.V and Q lung parameter maps based on three coronal slices were obtained at baseline and after 14 days (COPD patients) or after a short pause outside the scanner (healthy subjects). Regional ventilation (RVent) and imaging flow volume loops by cross-correlation (ccVent) were quantified. Q was normalized to the signal of the main pulmonary artery (Q) and quantified (Q). Pulmonary pulse wave transit time (pPTT), voxel-by-voxel (regional), and whole lung (global) ventilation defect percentage based on RVent (VDP) and ccVent (VDP), perfusion defect percentage (QDP), and ventilation/perfusion match based on RVent (VQM) and ccVent (VQM) were calculated.Regional V and Q were analyzed globally for each subject. Each parameter's median of scans 1 and 2 were assessed by Wilcoxon sign rank test. A parameter's repeatability was analyzed by Bland-Altman analyses, coefficients of variation, intraclass correlation coefficients (ICC), and power calculations. The regional voxel repeatability was examined by calculating the Sørensen-Dice coefficient.There was no bias and no significant differences between the first and second MRI for any parameters (P > 0.05). Coefficient of variation ranged from 2.26% (ccVent) to 19.31% (QDP), ICC from 0.93 (QDP) to 0.60 (pPTT), the smallest detectable difference was 0.002 ccVent. Regional comparison showed the highest overlap (84%) in VDP in healthy voxels and the lowest (53%) in VDP defect voxels.V and Q PREFUL-MRI parameters were repeatable over two scan sessions in both healthy controls and COPD patients.2 TECHNICAL EFFICACY STAGE: 2.© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.

Perfusion-weighted (Qw) noncontrast-enhanced proton lung MRI is a promising technique for assessment of pulmonary perfusion, but still requires validation.To improve perfusion-weighted phase-resolved functional lung (PREFUL)-MRI, to validate PREFUL with perfusion single photon emission computed tomography (SPECT) as a gold standard, and to compare PREFUL with dynamic contrast-enhanced (DCE)-MRI as a reference.Retrospective.Twenty patients with chronic obstructive pulmonary disease (COPD), 14 patients with cystic fibrosis (CF), and 21 patients with chronic thromboembolic pulmonary hypertension (CTEPH) were included.For PREFUL-MRI, a spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories sequence were used at 1.5T.PREFUL-MRI coronal slices were acquired in free-breathing. DCE-MRI was performed in breath-hold with injection of 0.03 mmol/kg bodyweight of gadoteric acid at a rate of 4 cc/s. Perfusion SPECT images were obtained for six CTEPH patients. Images were coregistered. An algorithm to define the appropriate PREFUL perfusion phase was developed using perfusion SPECT data. Perfusion defect percentages (QDP) and Qw-values were calculated for all methods. For PREFUL quantitative perfusion values (PREFUL) and for DCE pulmonary blood flow (PBF) was calculated.Obtained parameters were assessed using Pearson correlation and Bland-Altman analysis.Qw-SPECT correlated with Qw-DCE (r = 0.50, P < 0.01) and Qw-PREFUL (r = 0.47, P < 0.01). Spatial overlap of QDP maps showed an agreement ≥67.7% comparing SPECT and DCE, ≥64.1% for SPECT and PREFUL, and ≥60.2% comparing DCE and PREFUL. Significant correlations of Qw-PREFUL and Qw-DCE were found (COPD: r = 0.79, P < 0.01; CF: r = 0.77, P < 0.01; CTEPH: r = 0.73, P < 0.01). PREFUL /PBF correlations were similar/lower (CF, CTEPH: P > 0.12; COPD: P < 0.01) compared to Qw-PREFUL/DCE correlations. PREFUL -values were higher/similar compared to PBF-values (COPD, CF: P < 0.01; CTEPH: P = 0.026).The automated PREFUL algorithm may allow for noncontrast-enhanced pulmonary perfusion assessment in COPD, CF, and CTEPH patients comparable to DCE-MRI. Level of Evidence 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:103-114.© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.