Relationship of computed tomography-based measurements with symptom perception and quality of life in patients with severe asthma.

BACKGROUND: Symptom perception and quality of life (QOL) are important domains for properly managing severe asthma. This study aimed to assess the relationship between airway structural and parenchymal variables measured using chest computed tomography (CT) and subjective symptom perception and QOL in patients with severe asthma enrolled in the Korean Severe Asthma Registry. METHODS: This study used CT-based objective measurements, including airway wall thickness (WT), hydraulic diameter, functional small airway disease (fSAD), and emphysematous lung (Emph), to assess their association with subjective symptom (cough, dyspnea, wheezing, and sputum) perception measured using the visual analog scale, and QOL measured by the Severe Asthma Questionnaire (SAQ). RESULTS: A total of 94 patients with severe asthma were enrolled in this study. The WT and fSAD% were significantly positively associated with cough and dyspnea, respectively. For QOL, WT and Emph% showed significant negative associations with the SAQ. However, there was no significant association between lung function and symptom perception or between lung function and QOL. CONCLUSION: Overall, WT, fSAD%, and Emph% measured using chest CT were associated with subjective symptom perception and QOL in patients with severe asthma. This study provides a basis for clarifying the clinical correlates of imaging-derived metrics and for understanding the mechanisms of respiratory symptom perception.

Pulmonary MRI with hyperpolarized xenon-129 demonstrates novel alterations in gas transfer across the air-blood barrier in asthma.

BACKGROUND: Individuals with asthma can vary widely in clinical presentation, severity, and pathobiology. Hyperpolarized xenon-129 (Xe129) MRI is a novel imaging method to provide 3-D mapping of both ventilation and gas exchange in the human lung. PURPOSE: To evaluate the functional changes in adults with asthma as compared to healthy controls using Xe129 MRI. METHODS: All subjects (20 controls and 20 asthmatics) underwent lung function measurements and Xe129 MRI on the same day. Outcome measures included the pulmonary ventilation defect and transfer of inspired Xe129 into two soluble compartments: tissue and blood. Ten asthmatics underwent Xe129 MRI before and after bronchodilator to test whether gas transfer measures change with bronchodilator effects. RESULTS: Initial analysis of the results revealed striking differences in gas transfer measures based on age, hence we compared outcomes in younger (n = 24, ≤ 35 years) versus older (n = 16, > 45 years) asthmatics and controls. The younger asthmatics exhibited significantly lower Xe129 gas uptake by lung tissue (Asthmatic: 0.98% ± 0.24%, Control: 1.17% ± 0.12%, P = 0.035), and higher Xe129 gas transfer from tissue to the blood (Asthmatic: 0.40 ± 0.10, Control: 0.31% ± 0.03%, P = 0.035) than the younger controls. No significant difference in Xe129 gas transfer was observed in the older group between asthmatics and controls (P > 0.05). No significant change in Xe129 transfer was observed before and after bronchodilator treatment. CONCLUSIONS: By using Xe129 MRI, we discovered heterogeneous alterations of gas transfer that have associations with age. This finding suggests a heretofore unrecognized physiological derangement in the gas/tissue/blood interface in young adults with asthma that deserves further study.

Validation of computational fluid dynamics models for airway deposition with SPECT data of the same population.

This study compared computational fluid dynamic (CFD) model predictions on aerosol deposition in six asthmatic patients to the in-vivo results of the same group. Patient-specific ventilation and internal air distribution were prescribed using inspiratory and expiratory CT scans of each patient, accounting for individual lobar air flow distribution. Moreover, the significant influence of realistic mouth and throat geometries on regional deposition is demonstrated. The in-vivo data were obtained from single photon emission computed tomography (SPECT) in 6 subjects with mild asthma selected from a database of historical clinical trials. The governing flow and particle tracking equations were solved numerically using a commercial CFD tool, and the modeled deposition results were compared to the SPECT data. Good agreement was found between the CFD model, applying k-ω SST turbulence model, and SPECT in terms of aerosol deposition. The average difference for the lobar deposition obtained from CFD model and SPECT/CT data was 2.1%. The high level of agreement is due to applying patient specific airway geometries and inspiratory/expiratory CT images, anatomical upper airways, and realistic airway trees. The results of this study show that CFD is a powerful tool to simulate patient-specific deposition if correct boundary conditions are applied and can generate similar information obtained with functional imaging tools, such as SPECT.

Sampling pattern discrepancy in the application of compressed sensing hyperpolarized xenon-129 lung MRI.

Although hyperpolarized (HP) 129Xe ventilation MRI can be carried out within a breath hold, it is still challenging for many sick patients. Compressed sensing (CS) is a viable alternative to accelerate this approach. However, undersampled images with identical sampling ratios differ from one another. Twenty subjects (n = 10 healthy and n = 10 patients with asthma) were scanned using a GE MR750 3 T scanner, acquiring fully sampled 2D multi-slice HP 129Xe lung ventilation images (10 s breath hold, 128 × 80 (FE × PE-frequency encoding × phase encoding) and 16 slices). Using fully sampled data, 500 variable-density Cartesian random undersampling patterns were generated, each at eight different sampling ratios from 10% to 80%. The parallel imaging and compressed sensing (PICS) command from BART was employed to reconstruct undersampled data. The signal to noise ratio (SNR), structural similarity index measurement (SSIM) and sidelobe to peak ratio of each were subsequently compared. There was a high degree of variation in both SNR and SSIM results from each of the 500 masks of each sampling rate. As the undersampling increases, there is more variation in the quantifying metrics, for both healthy and asthmatic individuals. Our study shows that random undersampling poses a significant challenge when applied at sampling ratios less than 60%, despite fulfilling CS's incoherency criteria. Such low sampling ratios will result in a large variety of undersampling patterns. Therefore, skipped segments of k-space cannot be allowed to happen randomly at low sampling rates. By optimizing the sampling pattern, CS will reach its full potential and be able to be applied to a highly undersampled 129Xe lung dataset.

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

BACKGROUND: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. RESEARCH QUESTION: What are the most relevant changes in CT scan parameters over time for assessing response to treatment? STUDY DESIGN AND METHODS: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists anonymized to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated. RESULTS: Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24). INTERPRETATION: Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02273661; URL: www. CLINICALTRIALS: gov).

fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

Structural and functional features of asthma participants with fixed airway obstruction using CT imaging and 1D computational fluid dynamics: A feasibility study.

Asthma with fixed airway obstruction (FAO) is associated with significant morbidity and rapid decline in lung function, making its treatment challenging. Quantitative computed tomography (QCT) along with data postprocessing is a useful tool to obtain detailed information on airway structure, parenchymal function, and computational flow features. In this study, we aim to identify the structural and functional differences between asthma with and without FAO. The FAO group was defined by a ratio of forced expiratory volume in 1 s (FEV1 ) to forced vital capacity (FVC), FEV1 /FVC <0.7. Accordingly, we obtained two sets of QCT images at inspiration and expiration of asthma subjects without (N = 24) and with FAO (N = 12). Structural and functional QCT-derived airway variables were extracted, including normalized hydraulic diameter, normalized airway wall thickness, functional small airway disease, and emphysema percentage. A one-dimensional (1D) computational fluid dynamics (CFD) model considering airway deformation was used to compare the pressure distribution between the two groups. The computational pressures showed strong correlations with the pulmonary function test (PFT)-based metrics. In conclusion, asthma participants with FAO had worse lung functions and higher-pressure drops than those without FAO.

Semiautomated Segmentation and Analysis of Airway Lumen in Pediatric Patients Using Ultra Short Echo Time MRI.

RATIONALE AND OBJECTIVES: Ultra short echo time (UTE) magnetic resonance imaging (MRI) pulse sequences have shown promise for airway assessment, but the feasibility and repeatability in the pediatric lung are unknown. The purpose of this work was to develop a semiautomated UTE MRI airway segmentation pipeline from the trachea-to-tertiary airways in pediatric participants and assess repeatability and lumen diameter correlations to lung function. MATERIALS AND METHODS: A total of 29 participants (n = 7 healthy, n = 11 cystic fibrosis, n = 6 asthma, and n = 5 ex-preterm), aged 7-18 years, were imaged using a 3D stack-of-spirals UTE examination at 3 T. Two independent observers performed airway segmentations using a pipeline developed in-house; observer 1 repeated segmentations 1 month later. Segmentations were extracted using region-growing with leak detection, then manually edited if required. The airway trees were skeletonized, pruned, and labeled. Airway lumen diameter measurements were extracted using ray casting. Intra- and interobserver variability was assessed using the Sørensen-Dice coefficient (DSC) and intra-class correlation coefficient (ICC). Correlations between lumen diameter and pulmonary function were assessed using Spearman's correlation coefficient. RESULTS: For airway segmentations and lumen diameter, intra- and interobserver DSCs were 0.88 and 0.80, while ICCs were 0.95 and 0.89, respectively. The variability increased from the trachea-to-tertiary airways for intra- (DSC: 0.91-0.64; ICC: 0.91-0.49) and interobserver (DSC: 0.84-0.51; ICC: 0.89-0.21) measurements. Lumen diameter was significantly correlated with forced expiratory volume in 1 second and forced vital capacity (P < .05). CONCLUSION: UTE MRI airway segmentation from the trachea-to-tertiary airways in pediatric participants across a range of diseases is feasible. The UTE MRI-derived lumen measurements were repeatable and correlated with lung function.

Pleural line slope in point of care ultrasound assessment of paediatric wheeze may reflect respiratory effort.

AIM: Asthma scoring systems rely on physical examination findings. Point of care ultrasound may provide an objective means to document improvement in the work of breathing in paediatric lower airway obstruction. METHODS: Thirty children with wheeze on physical examination (cases) and 15 children presenting with abdominal pain (controls) were studied. Using point-of-care ultrasound, m-mode tracing of lung was recorded above the right hemidiaphragm at the midclavicular line. Pleural line slope and excursion were measured before and after treatment. RESULTS: Twenty patients had a final slope measurement under 20°, and only three were admitted-one for hypoxia that resolved prior to ascending to the ward and another for poor compliance. Average decrease in pleural line slope after treatment was 43% and average decrease in pleural line excursion was 32%. Of the 10 children admitted, 8 had measurements over 25°. The correlation coefficient between pleural slope and pleural excursion was 0.67. All controls had a horizontal m-mode tracing at the pleural line. CONCLUSION: Oscillation of the m-mode line at the pleura is seen in children with lower airway obstruction and is absent in controls. There appears to be a correlation between beta-agonist therapy and decreased pleural line slope and excursion.

Hyperpolarized 129Xe MRI, 99mTc scintigraphy, and SPECT in lung ventilation imaging: a quantitative comparison.

RATIONALE AND OBJECTIVES: The current clinical standard for functional imaging of patients with lung ailments is nuclear medicine scintigraphy and Single Photon Emission Computed Tomography (SPECT) which detect the gamma decay of inhaled radioactive tracers. Hyperpolarized (HP) Xenon-129 MRI (XeMRI) of the lungs has recently been FDA approved and provides similar functional images of the lungs with higher spatial resolution than scintigraphy and SPECT. Here we compare Technetium-99m (99mTc) diethylene-triamine-pentaacetate scintigraphy and SPECT with HP XeMRI in healthy controls, asthma, and chronic obstructive pulmonary disorder (COPD) patients. MATERIALS AND METHODS: 59 subjects, healthy, with asthma, and with COPD, underwent 99mTc scintigraphy/SPECT, standard spirometry, and HP XeMRI. XeMRI and SPECT images were registered for direct voxel-wise signal comparisons. Images were also compared using ventilation defect percentage (VDP), and a standard 6-compartment method. VDP calculated from XeMRI and SPECT images was compared to spirometry. RESULTS: Median Pearson correlation coefficient for voxel-wise signal comparison was 0.698 (0.613-0.782) between scintigraphy and XeMRI and 0.398 (0.286-0.502) between SPECT and XeMRI. Correlation between VDP measures was r = 0.853, p < 0.05. VDP separated asthma and COPD from the control group and was significantly correlated with FEV1, FEV1/FVC, and FEF 25-75. CONCLUSION: HP XeMRI provides equivalent information to 99mTc SPECT and standard spirometry measures. Additionally, XeMRI is non-invasive, hence it could be used for longitudinal studies for evaluating emerging treatment for lung ailments.

A Novel Air Trapping Segment Score Identifies Opposing Effects of Obesity and Eosinophilia on Air Trapping in Asthma.

Rationale: Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments. Objectives: To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. Methods: In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area. The resulting AT segment score (0-19) was related to patient outcomes. Measurements and Main Results: AT varied at the lung segment level and tended to persist at the patient and lung segment levels over 3 years. Patients with widespread AT (⩾10 segments) had more severe asthma (P < 0.05). The mean (±SD) AT segment score in patients with a body mass index ⩾30 kg/m2 was lower than in patients with a body mass index <30 kg/m2 (3.5 ± 4.6 vs. 5.5 ± 6.3; P = 0.008), and the frequency of AT in lower lobe segments in obese patients was less than in upper and middle lobe segments (35% vs. 46%; P = 0.001). The AT segment score in patients with sputum eosinophils ⩾2% was higher than in patients without sputum eosinophilia (7.0 ± 6.1 vs. 3.3 ± 4.9; P < 0.0001). Lung segments with AT more frequently had airway mucus plugging than lung segments without AT (48% vs. 18%; P ⩽ 0.0001). Conclusions: In patients with asthma, air trapping is more severe in those with airway eosinophilia and mucus plugging, whereas those who are obese have less severe trapping because their lower lobe segments are spared.

Measuring Anatomical Distributions of Ventilation and Aerosol Deposition with PET-CT.

In disease, lung function and structure are heterogeneous, and aerosol transport and local deposition vary significantly among parts of the lung. Understanding such heterogeneity is relevant to aerosol medicine and for quantifying mucociliary clearance from different parts of the lung. In this chapter, we describe positron emission tomography (PET) imaging methods to quantitatively assess the deposition of aerosol and ventilation distribution within the lung. The anatomical information from computed tomography (CT) combined with the PET-deposition data allows estimates of airway surface concentration and peripheral tissue dosing in bronchoconstricted asthmatic subjects. A theoretical framework is formulated to quantify the effects of heterogeneous ventilation, uneven aerosol ventilation distribution in bifurcations, and varying escape from individual airways along a path of the airway tree. The framework is applied to imaging data from bronchoconstricted asthmatics to assess the contributions of these factors to the unevenness in lobar deposition. Results from this analysis show that the heterogeneity of ventilation contributes on average to more than one-third of the variability in interlobar deposition. Actual contribution of ventilation in individual lungs was variable and dependent on the breathing rate used by the subject during aerosol inhalation; the highest contribution was in patients breathing slowly. In subjects breathing faster, contribution of ventilation was reduced, with more expanded lobes showing lower deposition per unit ventilation than less expanded ones in these subjects. The lobar change in expansion measured from two static CT scans, which is commonly used as a surrogate for ventilation, did not correlate with aerosol deposition or with PET-measured ventilation. This suggests that dynamic information is needed to provide proper estimates of ventilation for asthmatic subjects. We hope that the enhanced understanding of the causes of heterogeneity in airway and tissue dosing using the tools presented here will help to optimize therapeutic effectiveness of inhalation therapy while minimizing toxicity.

Asthma as an Inflammatory Reason of Tracheobronchial PSMA Uptake.

ABSTRACT: A 53-year-old man with persisting increased serum prostate-specific antigen level (9.53 ng/mL) and repeated negative prostate biopsies was referred for a PET/CT with 68 Ga-PSMA-11. The PET/CT revealed focal uptake in the prostate suggestive of localized prostate cancer. Incidentally, it also showed a diffuse uptake in the tracheobronchial tree suspicious for a benign etiology. Because of the clinical history of asthma exacerbation in the previous week, further supplementary studies were performed showing a pathological fractional exhaled nitric oxide level (92 ppb; reference values, <25 ppb) and mild airway obstruction in the spirometry. These findings confirmed asthma as an inflammatory etiology of the tracheobronchial PSMA uptake.

Tissue Doppler Echocardiography As A Predictor Of Early Subclinical Right Ventricular Diastolic Dysfunction In Asthmatic Children.

Objectives: To assess the effect of asthma in children on systolic and diastolic functions of the heart, and to explore the relationship between the two. Method: The case-controlstudy was conducted at Kafrelsheikh University Hospital, Egypt, from September 2019 to May 2022, and comprised asthmatic children of either gender aged 5-15 years and healthy controls matched for age and gender. The participants were subjected to detailed history, complete examination, spirometry evaluation and conventional and tissue Doppler echocardiography. Myocardial performance index was calculated and compared. Data was analysed using SPSS 22. RESULTS: Of the 120 subjects, 60(50%) were cases; 33(55%) boys and 27(45%) girls with mean age 9.4±2.9 years(range: 5-15 years). The remaining 60(50%)subjects were controls; 34(56.6%) boys and 26(43.3%) girls with mean age 9.7±2.9 years (range: 5-15 years). Left ventricular dimensions, estimated pulmonary artery pressure, and right ventricular dimensions showed no significant inter-group differences (p>0.05), but right ventricular end diastolic diameter was significantly higher in the cases than the controls (p=0.046). Tissue Doppler showed that lateral annular peak Ê, Â, isovolumetric relaxation time and myocardial performance index values were significantly different between the groups (p<0.05). CONCLUSIONS: Tissue Doppler echocardiography could detectsubtle right ventricular diastolic dysfunction in asthmatic children even with no clinical symptoms and normal findings on conventional echocardiography.

Effects of inhaled corticosteroids on brain volumetry, depression and anxiety-like behaviors in a rat model of asthma.

Brain functional deficits have been reported in asthma patients which can result in behavioral disorders like depression and anxiety. These deficits may be associated with factors like resistance to treatment, incorrect self-evaluation, and inadequate self-control. However, changes in the brain volume in allergic asthma and the effects of inhaled corticosteroids, the most common anti-inflammatory agents for asthma treatment, on these alterations remain largely unclear. Here, we evaluated depression and anxiety-like behavior as well as volume changes in different brain area, using magnetic resonance imaging in an animal model of allergic asthma with pretreatment of inhaled fluticasone propionate. Asthma-induced behavioral changes were partially, but not completely, prevented by pretreatment with inhaled fluticasone propionate. Volumetry findings showed that the allergen decreased volumes of the corpus callosum and subcortical white matter, as well as the septal region and hippocampus (especially CA1 and fimbria). However, volumes of neocortex, insular, and anterior cingulate cortex increased in asthmatic rats compared to controls. Namely, pretreatment with inhaled fluticasone propionate partially prevented asthma-induced brain volume changes, but not completely. These findings suggest that asthma is associated with structural alterations in the brain, which may contribute to the induction of psychological disorders. Thus, considering brain changes in the clinical assessments could have important implications for asthma treatment.

Quantitative analysis of lung function and airway remodeling using ventilation/perfusion single photon emission tomography/computed tomography and HRCT in patients with chronic obstructive pulmonary disease and asthma.

OBJECTIVE: To investigate the role of V/P SPECT/CT and HRCT quantitative parameters in evaluating COPD and asthma disease severity, airway obstructivity-grade, ventilation and perfusion distribution patterns, airway remodeling, and lung parenchymal changes. METHOD: Fifty-three subjects who underwent V/P SPECT/CT, HRCT, and pulmonary function tests (PFTs) were included. Preserved lung ventilation (PLVF), perfusion function (PLPF), airway obstructivity-grade (OG), proportion of anatomical volume, ventilation and perfusion contribution of each lobe, and V/P distribution patterns were evaluated using V/P SPECT/CT. The quantitative parameters of HRCT included CT bronchial and CT pulmonary function parameters. In addition, the correlation and difference of V/P SPECT/CT-, HRCT-, and PFT-related parameters were compared. RESULTS: There was a statistically significant difference between severe asthma and severe-very severe COPD in CT bronchial parameters, like WA, LA and AA, in the lung segment airways (P < 0.05). CT bronchial parameters, like as WT and WA, were statistically significant (p < 0.05) among asthma patients. The EI of severe-very severe COPD was different from that of the disease severity groups in asthma patients (P < 0.05). The airway obstructivity-grade, PLVF and PLPF differed significantly among the severe-very severe COPD and mild-moderate asthma patients (P < 0.05). And the PLPF was statistically significant among the disease severity groups in asthma and COPD (P < 0.05). OG and PLVF, PLPF, and PFT parameters were significantly correlated, with the FEV1 correlation being the most significant (r = - 0.901, r = 0.915, and r = 0.836, respectively; P < 0.01). There was a strong negative correlation between OG and PLVF (r = - 0.945) and OG and PLPF (r = - 0.853) and a strong positive correlation between PLPF and PLVF (r = 0.872). In addition, OG, PLVF, and PLPF were moderately to strongly correlated with CT lung function parameters (r = - 0.673 to - 0.839; P < 0.01), while lowly to moderately correlated with most CT bronchial parameters (r = - 0.366 to - 0.663, P < 0.01). There were three different V/P distribution patterns, including matched, mismatched, and reverse mismatched patterns. Last, the CT volume overestimated the contribution in the upper lobes and underestimated the lower lobes' contribution to overall function. CONCLUSIONS: Quantitative assessment of ventilation and perfusion abnormalities and the degree of pulmonary functional loss by V/P SPECT/CT shows promise as an objective measure to assess the severity of disease and lung function to guide localized treatments. There are differences between HRCT parameters and SPECT/CT parameters among the disease severity groups in asthma and COPD, which may enhance, to some extent, the understanding of complex physiological mechanisms in asthma and COPD.

Emergent Inflammatory Markers and Echocardiographic Indices in Patients with Bronchial Asthma.

Asthma is a heterogeneous disease, characterized by chronic inflammation and oxidative stress of the airways. Several inflammatory pathways including activation of the receptor for advanced glycation end products (RAGE) have been described in the course of the disease. DJ-1 is a redox-sensitive protein with multifaceted roles in mast cell homeostasis and an emerging role in the pathogenesis of asthma. Moreover, cardiac function abnormalities have been described via echocardiography in patients with asthma. The main aim of this study was to investigate the plasma levels of RAGE, its ligands and DJ-1 in asthmatic patients pre- and post-treatment along with echocardiographic indices of cardiovascular function. The study population was divided into two groups. Group A included 13 patients with newly diagnosed bronchial asthma who were free of treatment for at least two weeks and Group B included 12 patients without asthma. An echocardiography examination was performed on all patients. The plasma levels of RAGE, its ligands (AGEs, S100A12, S100B, S100A8/A9), the interleukins (IL-6, IL-1ß) and DJ-1 were measured. No differences were noted among the two groups for baseline characteristics and echocardiographic indices of cardiac function. In Group A, 31% suffered from mild asthma, 54% from moderate asthma and 15% from severe asthma. Plasma levels of IL-6, AGEs and AGE/RAGE ratio were increased and those of S100A12 and DJ-1 were decreased in asthmatics. Pharmacotherapy with corticosteroids/ß2-agonists decreased IL-6, and AGEs, and increased DJ-1. In search of novel approaches in diagnosing and treating patients with asthma, S100A12, ratio AGE/sRAGE, and DJ-1 in addition to IL-6 may prove to be useful tools.

The effects of benralizumab on airway geometry and dynamics in severe eosinophilic asthma: a single-arm study design exploring a functional respiratory imaging approach.

BACKGROUND: Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution. METHODS: BURAN is an interventional, single-arm, open-label, uncontrolled, prospective, multicentre study during which participants will receive three 30 mg subcutaneous doses of benralizumab at 4-week intervals. This study will use functional respiratory imaging (FRI), a novel, quantitative method of assessing patients' lung structure and function based on detailed, three-dimensional models of the airways, with direct comparison of images taken at Weeks 0 and 13. Patients aged ≥ 18 years with established SEA who may be receiving oral corticosteroids and/or other asthma controller medications, who are inadequately controlled on inhaled corticosteroid-long-acting ß2-agonist therapies and who have had ≥ 2 asthma exacerbations in the previous 12 months will be included. The objectives of BURAN are to describe changes in airway geometry and dynamics, measured by specific image-based airway volume and other FRI endpoints, following benralizumab therapy. Outcomes will be evaluated using descriptive statistics. Changes in FRI parameters, mucus plugging scores and central/peripheral ratio will be quantified as mean percent change from baseline (Week 0) to Week 13 (± 5 days) and statistical significance will be evaluated using paired t-tests. Relationships between FRI parameters/mucus plugging scores and conventional lung function measurements at baseline will be assessed with linear regression analyses for associations between outcomes, scatterplots to visualise the relationship, and correlation coefficients (Spearman's rank and Pearson's) to quantify the strength of these associations. CONCLUSIONS: The BURAN study will represent one of the first applications of FRI-a novel, non-invasive, highly sensitive method of assessing lung structure, function and health-in the field of biologic respiratory therapies. Findings from this study will increase understanding of cellular-level eosinophil depletion mechanisms and improvements in lung function and asthma control following benralizumab treatment. Trial registration EudraCT: 2022-000152-11 and NCT05552508.