Quantitative CT lung densitometry as an obstructive marker for the diagnosis of bronchiolitis obliterans in children.
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ABSTRACT:
SUBMITTER: Lee HJ
PROVIDER: S-EPMC9262182 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:To investigate the feasibility of CT-based quantitative airway and air-trapping measurements and to assess their correlation with pulmonary function in children with post-infectious bronchiolitis obliterans (PIBO). MATERIALS AND METHODS:This retrospective study approved by the institutional review board included chest CT scans and pulmonary function tests (PFT) completed between January 2005 and December 2016 in children diagnosed with PIBO. The quantitative analysis of segmental and subsegmental bronchi was performed on each chest CT scan, measuring the areas or diameters of lumens, walls, or the entire airway. The air-trapping volume (ATV), the volume of lung area exhibiting lower attenuation than the mean attenuation of normal and air-trapping areas, was also measured in each lobe. Comparison analyses between CT parameters and PFT results were performed with Pearson or Spearman correlation. RESULTS:In total, 23 patients were enrolled (mean age 7.0 ± 3.3 years; range, 4-15 years). We successfully measured 89.6% of all segmental bronchi. In the airway analysis, wall area showed a negative correlation with forced expiratory volume in one second (FEV1) in the majority of the pulmonary lobes. Air-trapping analyses demonstrated that ATV was negatively correlated with FEV1 and positively correlated with reactance at 5 Hz. CONCLUSION:Quantitative airway and air-trapping measurements from chest CT are feasible and correlate with pulmonary function in pediatric PIBO patients.
| S-EPMC6443232 | biostudies-literature
Project description:Bronchiolitis obliterans syndrome (BOS) is considered an airway-centered disease, with bronchiolitis obliterans (BO) as pathologic hallmark. However, the histologic spectrum of pure clinical BOS remains poorly characterized. We provide the first in-depth histopathologic description of well-characterized BOS patients and patients without chronic lung allograft dysfunction (CLAD), defined according to the recent consensus guidelines. Explant lung tissue from 52 clinically-defined BOS and 26 non-CLAD patients (collected 1993-2018) was analyzed for histologic parameters, including but not limited to airway lesions, vasculopathy and fibrosis. In BOS, BO lesions were evident in 38 (73%) patients and varied from concentric sub-epithelial fibrotic BO to inflammatory BO, while 10/14 patients without BO displayed 'vanishing airways', defined by a discordance between arteries and airways. Chronic vascular abnormalities were detected in 22 (42%) patients. Ashcroft fibrosis scores revealed a median of 43% (IQR: 23-69) of normal lung parenchyma per patient; 26% (IQR: 18-37) of minimal alveolar fibrous thickening; and 11% (IQR: 4-18) of moderate alveolar thickening without architectural damage. Patchy areas of definite fibrotic damage to the lung structure (i.e., Ashcroft score ≥5) were present in 28 (54%) patients. Fibrosis was classified as bronchocentric (n = 21/28, 75%), paraseptal (n = 17/28, 61%) and subpleural (n = 15/28, 54%). In non-CLAD patients, BO lesions were absent, chronic vascular abnormalities present in 1 (4%) patient and mean Ashcroft scores were significantly lower compared to BOS (p = 0.0038) with 78% (IQR: 64-88) normally preserved lung parenchyma. BOS explant lungs revealed evidence of various histopathologic findings, including vasculopathy and fibrotic changes, which may contribute to the pathophysiology of BOS.
| S-EPMC8745215 | biostudies-literature
Project description:Post-infectious bronchiolitis obliterans (BO) could be diagnosed via spirometry and chest computed tomography (CT); however, these tests are limited in infants. We aimed to evaluate the utility of lung clearance index (LCI) and air-trapping lung volume from chest CT in infants. This prospective study included 20 infants (mean age, 10.9 ± 6.3 months) diagnosed with post-infectious BO between 2009 and 2016. All subjects underwent multiple breath washout tests. For quantitative analysis of chest CT, the mean lung area attenuation value was used as an individual cutoff to determine the air-trapping lung volume. The mean cutoff lung attenuation value was -659 Hounsfield units, the mean total lung volume was 265 ml, and the mean air-trapping lung volume percentage was 22.9%. Functional residual capacity correlated with total lung volume and normal attenuation lung volume (p < 0.02). LCI (p < 0.02) and moment ratio (MR) 1 (p < 0.05) correlated with the air-trapping lung volume percentage. The concordance indices of LCI (0.659, p = 0.025) and MR1 (0.642, p = 0.046) were significantly correlated with the air-trapping lung volume percentage from CT. LCI and quantitative air-trapping lung volume from chest CT are feasible, complimentary tools for assessing infants with post-infectious BO.
| S-EPMC5680196 | biostudies-literature
Project description:BackgroundLung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung allograft dysfunction, in particular bronchiolitis obliterans syndrome (BOS). Although there is no approved or standard treatment for BOS, which may have several distinct phenotypes, extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment.MethodsWe reviewed all relevant clinical data indexed on PubMed from 1987 to 2017 to evaluate the role of ECP in patients with BOS.ResultsSeven small studies investigated the immunomodulatory effects of ECP in patients after solid organ transplant, and 12 studies reported clinical data specific to ECP therapy for BOS. Studies indicate that ECP triggers an apoptotic cellular cascade that exerts various immunomodulatory effects mediated via increases in anti-inflammatory cytokines, a decrease in proinflammatory cytokines, and an increase in tolerogenic regulatory T cells. Clinical evidence derived from relatively small single-center studies suggests that ECP therapy is associated with improvement or stabilization in lung function and sustainable, statistically significant, decreases in the rate of lung function decline in patients with BOS. Additionally, when adverse event data were reported, ECP was generally well tolerated. None of the comparative studies were randomized.ConclusionsImmunomodulation mediated via ECP is a rational therapeutic option that may improve clinical outcomes in patients with BOS, particularly in the context of in-depth patient phenotyping as part of a stratified approach to treatment; good quality randomized controlled trials are needed to confirm observational findings.
| S-EPMC7228625 | biostudies-literature
Project description:Asthma and postinfectious bronchiolitis obliterans (PIBO) are chronic lung diseases characterized by recurrent episodes of wheezing. Mycoplasma, adenovirus, and respiratory syncytial virus infections can trigger both asthma and PIBO. These two diseases have common etiologic mechanisms that cause airway epithelial injury. They are often difficult to differentiate clinically in preschool children because both are exacerbated by viral infections and respond similarly to steroids and β2 agonists. PIBO, which is occasionally observed in children, is diagnosed through characteristic findings of air trapping on computed tomography or in biopsy samples of lung tissue. However, researchers have not clearly identified the specific blood markers that can distinguish these diseases or the differences in the mechanisms of development. We performed proteomic analysis of plasma to identify specific biomarkers that can be helpful in differentiating asthma from PIBO. This study discovered plasma biomarker candidates by measuring plasma proteome sequential window acquisition of all theoretical mass spectra (SWATH-MS) and included 30 healthy children, 18 with asthma and 15 with PIBO. was used to measure proteins in plasma samples. We identified and quantified 354 proteins across all 63 samples in the SWATH-MS analysis.
2022-12-01 | PXD034996 | Pride
Project description:Background and purposeIntracerebral hemorrhage growth independently predicts disability and death. We hypothesized that noncontrast quantitative CT densitometry reflects active bleeding and improves predictive models of growth.Materials and methodsWe analyzed 81 of the 96 available baseline CT scans obtained <3 hours post-ICH from the placebo arm of the phase IIb trial of recombinant factor VIIa. Fifteen scans could not be analyzed for technical reasons, but baseline characteristics were not statistically significantly different. Hounsfield unit histograms for each ICH were generated. Analyzed qCTD parameters included the following: mean, SD, coefficient of variation, skewness (distribution asymmetry), and kurtosis ("peakedness" versus "flatness"). These densitometry parameters were examined in statistical models accounting for baseline volume and time-to-scan.ResultsThe coefficient of variation of the ICH attenuation was the most significant individual predictor of hematoma growth (adjusted R(2) = 0.107, P = .002), superior to BV (adjusted R(2) = 0.08, P = .006) or TTS (adjusted R(2) = 0.03, P = .05). The most significant combined model incorporated coefficient of variation, BV, and TTS (adjusted R(2) = 0.202, P = .009 for coefficient of variation) compared with BV and TTS alone (adjusted R(2) = 0.115, P < .05). qCTD increased the number of growth predictions within ±1 mL of actual 24-hour growth by up to 47%.ConclusionsHeterogeneous ICH attenuation on hyperacute (<3 hours) CT imaging is predictive of subsequent hematoma expansion and may reflect an active bleeding process. Further studies are required to determine whether qCTD can be incorporated into standard imaging protocols for predicting ICH growth.
| S-EPMC7964597 | biostudies-literature
Project description:RationaleDespite the importance of bronchiolitis obliterans syndrome (BOS) in lung transplantation, little is known regarding the factors that influence survival after the onset of this condition, particularly among bilateral transplant recipients.ObjectivesTo identify factors that influence survival after the onset of BOS among bilateral lung transplant recipients.MethodsThe effect of demographic or clinical factors, occurring before BOS, upon survival after the onset of BOS was studied in 95 bilateral lung transplant recipient using Cox proportional hazards models.Measurements and main resultsAlthough many factors, including prior acute rejection or rejection treatments, were not associated with survival after BOS, BOS onset within 2 years of transplantation (early-onset BOS), or BOS onset grade of 2 or 3 (high-grade onset) were predictive of significantly worse survival (early onset P = 0.04; hazard ratio, 1.84; 95% confidence interval, 1.03-3.29; high-grade onset P = 0.003; hazard ratio, 2.40; 95% confidence interval, 1.34-4.32). The effects of both early onset and high-grade onset on survival persisted in multivariable analysis and after adjustment for concurrent treatments. Results suggested an interaction might exist between early onset and high-grade onset. In particular, high-grade onset of BOS, regardless of its timing after transplant, is associated with a very poor prognosis.ConclusionsThe course of BOS after bilateral lung transplantation is variable. Distinct patterns of survival after BOS are evident and related to timing or severity of onset. Further characterization of these subgroups should provide a more rational basis from which to design, stratify, and assess response in future BOS treatment trials.
| S-EPMC2949403 | biostudies-literature
Project description:Oxygen-sensitive 3He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO2) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients.
| S-EPMC2755794 | biostudies-other
Project description:ObjectiveThe objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome.Experimental designBronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis.ResultsThe average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/-0.02, average+/-SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/-0.09, average+/-SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome.ConclusionsBronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.
| S-EPMC3879344 | biostudies-literature
Project description:Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS; however, quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory computed tomography [CT] scans) in lung transplant recipients diagnosed with BOS (n = 20) and time-matched stable lung transplant recipients (n = 20). Serial PRM measurements were performed prediagnosis, at time of BOS diagnosis, and postdiagnosis (Tpre , T0 , and Tpost , respectively), or at a postoperatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. Using PRM, we observed an increase in functional small airway disease (fSAD), from Tpre to T0 (p = 0.006) and a concurrent decrease in healthy parenchyma (p = 0.02) in the BOS group. This change in PRM continued to Tpost , which was significantly different compared to the stable patients (p = 0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in forced expiratory volume in 1 s (p = 0.011). Micro-CT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate output to monitor BOS progression in lung transplant recipients.
| S-EPMC5083149 | biostudies-literature