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1.
Sci Rep ; 14(1): 5492, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448648

RESUMO

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.


Assuntos
Asma , Laringe , Humanos , Hidrodinâmica , Tomografia Computadorizada de Emissão de Fóton Único , Nariz , Asma/diagnóstico por imagem , Aerossóis e Gotículas Respiratórios
2.
Med Phys ; 51(4): 2413-2423, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431967

RESUMO

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.


Assuntos
Asma , Broncodilatadores , Adulto Jovem , Humanos , Adulto , Broncodilatadores/uso terapêutico , Barreira Alveolocapilar , Pulmão/diagnóstico por imagem , Asma/diagnóstico por imagem , Asma/tratamento farmacológico , Isótopos de Xenônio , Imageamento por Ressonância Magnética/métodos , Xenônio/uso terapêutico
3.
Respir Med ; 225: 107598, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38499273

RESUMO

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.


Assuntos
Asma , Enfisema , Doença Pulmonar Obstrutiva Crônica , Humanos , Qualidade de Vida , Asma/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Dispneia/etiologia , Tosse/etiologia , Percepção
4.
Psychophysiology ; 61(5): e14513, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38339852

RESUMO

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.


Assuntos
Asma , Imageamento por Ressonância Magnética , Humanos , Óxido Nítrico/análise , Oxigênio , Asma/diagnóstico por imagem , Emoções/fisiologia
5.
Physiol Rep ; 12(1): e15909, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38185478

RESUMO

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.


Assuntos
Obstrução das Vias Respiratórias , Asma , Humanos , Estudos de Viabilidade , Hidrodinâmica , Asma/complicações , Asma/diagnóstico por imagem , Obstrução das Vias Respiratórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X
6.
Acad Radiol ; 31(2): 648-659, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37550154

RESUMO

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.


Assuntos
Asma , Fibrose Cística , Recém-Nascido , Humanos , Criança , Imageamento Tridimensional/métodos , Pulmão/diagnóstico por imagem , Asma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
7.
J Aerosol Med Pulm Drug Deliv ; 36(4): 210-227, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37585546

RESUMO

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.


Assuntos
Asma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Administração por Inalação , Aerossóis e Gotículas Respiratórios , Pulmão/diagnóstico por imagem , Asma/diagnóstico por imagem
9.
Clin Nucl Med ; 48(10): e494-e495, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37566807

RESUMO

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.


Assuntos
Asma , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Oligopeptídeos , Ácido Edético , Radioisótopos de Gálio , Neoplasias da Próstata/patologia , Asma/complicações , Asma/diagnóstico por imagem
10.
J Pak Med Assoc ; 73(Suppl 4)(4): S151-S155, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37482849

RESUMO

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.


Assuntos
Asma , Disfunção Ventricular Direita , Masculino , Feminino , Humanos , Criança , Ecocardiografia Doppler/métodos , Asma/complicações , Asma/diagnóstico por imagem , Ecocardiografia , Diástole , Ventrículos do Coração/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem
11.
Respir Physiol Neurobiol ; 315: 104121, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37473791

RESUMO

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.


Assuntos
Antiasmáticos , Asma , Animais , Ratos , Depressão/diagnóstico por imagem , Depressão/tratamento farmacológico , Androstadienos/uso terapêutico , Administração por Inalação , Asma/diagnóstico por imagem , Asma/tratamento farmacológico , Fluticasona/uso terapêutico , Corticosteroides/uso terapêutico , Encéfalo/diagnóstico por imagem , Ansiedade/diagnóstico por imagem , Ansiedade/tratamento farmacológico
12.
Ann Nucl Med ; 37(9): 504-516, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37268867

RESUMO

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.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Remodelação das Vias Aéreas , Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Asma/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Perfusão
13.
Biomolecules ; 13(6)2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37371535

RESUMO

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.


Assuntos
Asma , Proteína S100A12 , Humanos , Ligantes , Interleucina-6 , Receptor para Produtos Finais de Glicação Avançada , Produtos Finais de Glicação Avançada , Asma/diagnóstico por imagem , Asma/tratamento farmacológico , Ecocardiografia
14.
Respir Res ; 24(1): 121, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37131265

RESUMO

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.


Assuntos
Asma , Eosinofilia Pulmonar , Humanos , Estudos Prospectivos , Asma/diagnóstico por imagem , Asma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Eosinofilia Pulmonar/diagnóstico por imagem , Eosinofilia Pulmonar/tratamento farmacológico , Inflamação
15.
Am J Respir Cell Mol Biol ; 69(1): 13-21, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37017484

RESUMO

Asthma is a chronic inflammatory airway disease driven by various infiltrating immune cell types into the lung. Optical microscopy has been used to study immune infiltrates in asthmatic lungs. Confocal laser scanning microscopy (CLSM) identifies the phenotypes and locations of individual immune cells in lung tissue sections by employing high-magnification objectives and multiplex immunofluorescence staining. In contrast, light-sheet fluorescence microscopy (LSFM) can visualize the macroscopic and mesoscopic architecture of whole-mount lung tissues in three dimensions (3D) by adopting an optical tissue-clearing method. Despite each microscopy method producing image data with unique resolution from a tissue sample, CLSM and LSFM have not been applied together because of different tissue-preparation procedures. Here, we introduce a new approach combining LSFM and CLSM into a sequential imaging pipeline. We built a new optical tissue clearing workflow in which the immersion clearing agent can be switched from an organic solvent to an aqueous sugar solution for sequential 3D LSFM and CLSM of mouse lungs. This sequential combination microscopy offered quantitative 3D spatial analyses of the distribution of immune infiltrates in the same mouse asthmatic lung tissue at the organ, tissue, and cell levels. These results show that our method facilitates multiresolution 3D fluorescence microscopy as a new imaging approach providing comprehensive spatial information for a better understanding of inflammatory lung diseases.


Assuntos
Asma , Imageamento Tridimensional , Animais , Camundongos , Imageamento Tridimensional/métodos , Microscopia de Fluorescência/métodos , Pulmão/diagnóstico por imagem , Asma/diagnóstico por imagem , Microscopia Confocal/métodos
16.
Acad Radiol ; 30(12): 3114-3123, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37032278

RESUMO

RATIONALE AND OBJECTIVES: The minimal clinically important difference (MCID) and upper limit of normal (ULN) for MRI ventilation defect percent (VDP) were previously reported for hyperpolarized 3He gas MRI. Hyperpolarized 129Xe VDP is more sensitive to airway dysfunction than 3He, therefore the objective of this study was to determine the ULN and MCID for 129Xe MRI VDP in healthy and asthma participants. MATERIALS AND METHODS: We retrospectively evaluated healthy and asthma participants who underwent spirometry and 129XeMRI on a single visit; participants with asthma completed the asthma control questionnaire (ACQ-7). The MCID was estimated using distribution- (smallest detectable difference [SDD]) and anchor-based (ACQ-7) methods. Two observers measured VDP (semiautomated k-means-cluster segmentation algorithm) in 10 participants with asthma, five-times each in random order, to determine SDD. The ULN was estimated based on the 95% confidence interval of the relationships between VDP and age. RESULTS: Mean VDP was 1.6 ± 1.2% for healthy (n = 27) and 13.7 ± 12.9% for asthma participants (n = 55). ACQ-7 and VDP were correlated (r = .37, p = .006; VDP = 3.5·ACQ + 4.9). The anchor-based MCID was 1.75% while the mean SDD and distribution-based MCID was 2.25%. VDP was correlated with age for healthy participants (p = .56, p =.003; VDP = .04·Age-.01). The ULN for all healthy participants was 2.0%. By age tertiles, the ULN was 1.3% ages 18-39 years, 2.5% for 40-59 years and 3.8% for 60-79 years. CONCLUSION: The 129Xe MRI VDP MCID was estimated in participants with asthma; the ULN was estimated in healthy participants across a range of ages, both of which provide a way to interpret VDP measurements in clinical investigations.


Assuntos
Asma , Pulmão , Humanos , Lactente , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Diferença Mínima Clinicamente Importante , Asma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
17.
Zhongguo Zhen Jiu ; 43(4): 439-43, 2023 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-37068822

RESUMO

OBJECTIVE: To detect the body surface temperature of the relevant back-shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back-shu points under the condition of lung disease. METHODS: Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography. RESULTS: The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group (P<0.01, P<0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups (P<0.01, P<0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) (P>0.05). CONCLUSION: The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.


Assuntos
Terapia por Acupuntura , Asma , Meridianos , Humanos , Temperatura , Asma/diagnóstico por imagem , Pontos de Acupuntura , Terapia por Acupuntura/métodos
18.
Allergol Int ; 72(3): 428-436, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36997391

RESUMO

BACKGROUND: Although paranasal sinuses are one of the most representative organs affected by eosinophilic granulomatosis with polyangiitis (EGPA), they have not been studied sufficiently. The aim of this study was to compare computed tomography (CT) findings in paranasal sinuses of EGPA with those of other eosinophilic sinus diseases and elucidate the clinical relevance of their severity. METHODS: CT findings of paranasal sinuses in EGPA patients prior to therapeutic intervention (n = 30) were evaluated using the Lund-Mackay staging (LMS) system and compared with those of three control diseases [(NSAID-exacerbated respiratory disease (N-ERD), aspirin-tolerant asthma, and eosinophilic chronic rhinosinusitis without asthma (ECRS)]. We divided EGPA patients into three groups based on their LMS scores and examined their association with disease manifestation. RESULTS: Total scores of the LMS system in EGPA were significantly lower than those of N-ERD and ECRS without asthma. There was a large variation in total LMS scores in EGPA, suggesting considerable heterogeneity of their sinus lesions. Although EGPA with low LMS system scores showed only minor findings in maxillary and anterior ethmoid regions, those with high LMS system scores were characterized by high scores in the ostiomeatal complex. However, the frequencies of patients with a Five-Factor Score ≥2 and with cardiac involvement were significantly higher for EGPA with low LMS system scores. CONCLUSIONS: Although paranasal sinus lesions in EGPA were less severe than those of other eosinophilic sinus diseases, their milder CT findings may be associated with a higher frequency of extra-respiratory organ involvement.


Assuntos
Asma , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Seios Paranasais , Humanos , Granulomatose com Poliangiite/diagnóstico por imagem , Granulomatose com Poliangiite/complicações , Síndrome de Churg-Strauss/diagnóstico por imagem , Síndrome de Churg-Strauss/tratamento farmacológico , Relevância Clínica , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/patologia , Asma/diagnóstico por imagem , Asma/complicações , Tomografia Computadorizada por Raios X , Tomografia
19.
Br J Radiol ; 96(1146): 20220630, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36752590

RESUMO

The need for airway imaging is defined by the limited sensitivity of common clinical tests like spirometry, lung diffusion (DLCO) and blood gas analysis to early changes of peripheral airways and to inhomogeneous regional distribution of lung function deficits. Therefore, X-ray and computed tomography (CT) are frequently used to complement the standard tests.As an alternative, magnetic resonance imaging (MRI) offers radiation-free lung imaging, but at lower spatial resolution. Non-contrast enhanced MRI shows healthy airways down to the first subsegmental level/4th order (CT: eighth). Bronchiectasis can be identified by wall thickening and fluid accumulation. Smaller airways become visible, when altered by peribronchiolar inflammation or mucus retention (tree-in-bud sign).The strength of MRI is functional imaging. Dynamic, time-resolved MRI directly visualizes expiratory airway collapse down to the lobar level (CT: segmental level). Obstruction of even smaller airways becomes visible as air trapping on the expiratory scans. MRI with hyperpolarized noble gases (3He, 129Xe) directly shows the large airways and peripheral lung ventilation. Dynamic contrast-enhanced MRI (DCE MRI) indirectly shows airway dysfunction as perfusion deficits resulting from hypoxic vasoconstriction of the dependent lung volumes. Further promising scientific approaches such as non-contrast enhanced, ventilation-/perfusion-weighted MRI from periodic signal changes of respiration and blood flow are in development.In summary, MRI of the lungs and airways excels with its unique combination of morphologic and functional imaging capacities for research (e.g., in chronic obstructive lung disease or asthma) as well as for clinical imaging (e.g., in cystic fibrosis).


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão/diagnóstico por imagem , Asma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Respiração
20.
Chest ; 164(1): 27-38, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36781102

RESUMO

BACKGROUND: We previously showed in patients with poorly controlled eosinophilic asthma that a single dose of benralizumab resulted in significantly improved Asthma Control Questionnaire (ACQ-6) score and 129Xe MRI ventilation defect percent (VDP) 28 days postinjection, and 129Xe MRI VDP and CT airway mucus occlusions were shown to independently predict this early ACQ-6 response to benralizumab. RESEARCH QUESTION: Do early VDP responses at 28 days persist, and do FEV1, fractional exhaled nitric oxide, and mucus plug score improve during a 2.5 year treatment period? STUDY DESIGN AND METHODS: Participants with poorly controlled eosinophilic asthma completed spirometry, ACQ-6, and MRI, 28 days, 1 year, and 2.5 years after initiation of treatment with benralizumab; chest CT was acquired at enrollment and 2.5 years later. RESULTS: Of 29 participants evaluated at 28 days post-benralizumab, 16 participants returned for follow-up while on therapy at 1 year, and 13 participants were evaluable while on therapy at 2.5 years post-benralizumab initiation. As compared with 28 days post-benralizumab, ACQ-6 score (2.0 ± 1.4) significantly improved after 1 year (0.5 ± 0.6, P = .02; 95% CI, 0.1-1.1) and 2.5 years (0.5 ± 0.5, P = .03; 95% CI, 0.1-1.1). The mean VDP change at 2.5 years (-4% ± 3%) was greater than the minimal clinically important difference, but not significantly different from VDP measured 28 days post-benralizumab. Mucus score (3 ± 4) was significantly improved at 2.5 years (1 ± 1, P = .03; 95% CI, 0.3-5.5). In six of eight participants with previous occlusions, mucus plugs vanished or substantially diminished 2.5 years later. VDP (P < .001) and mucus score (P < .001) measured at baseline, but not fractional exhaled nitric oxide or FEV1, independently predicted ACQ-6 score after 2.5 years. INTERPRETATION: In poorly controlled eosinophilic asthma, early MRI VDP responses at 28 days post-benralizumab persisted 2.5 years later, alongside significantly improved mucus scores and asthma control.


Assuntos
Obstrução das Vias Respiratórias , Antiasmáticos , Asma , Eosinofilia Pulmonar , Humanos , Óxido Nítrico , Asma/diagnóstico por imagem , Asma/tratamento farmacológico , Eosinofilia Pulmonar/tratamento farmacológico , Muco , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X , Antiasmáticos/uso terapêutico
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