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Regional ventilation changes in severe asthma after bronchial thermoplasty with (3)He MR imaging and CT.

ABSTRACT: To quantify regional lung ventilation in healthy volunteers and patients with severe asthma (both before and after thermoplasty) by using a combination of helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT), with the intention of developing more effective image-guided treatments for obstructive lung diseases.With approval of the local institutional review board, informed consent, and an Investigational New Drug Exemption, six healthy volunteers and 10 patients with severe asthma were imaged in compliance with HIPAA regulations by using both multidetector CT and (3)He MR imaging. Individual bronchopulmonary segments were labeled voxel by voxel from the CT images and then registered to the (3)He MR images by using custom software. The (3)He signal intensity was then analyzed by evaluating the volume-weighted fraction of total-lung signal intensity present in each segment (segmental ventilation percentage [ SVP segmental ventilation percentage ]) and by identifying the whole-lung defect percentage and the segmental defect percentage. Of the 10 patients with asthma, seven received treatment with bronchial thermoplasty and were imaged with (3)He MR a second time. Changes in segmental defect percentages and whole-lung defect percentages are presented.Ventilation measures for healthy volunteers yielded smaller segment-to-segment variation (mean SVP segmental ventilation percentage , 100% ± 18 [standard deviation]) than did the measures for patients with severe asthma (mean SVP segmental ventilation percentage , 97% ± 23). Patients with asthma also demonstrated larger segmental defect percentages (median, 13.5%; interquartile range, 8.9%-17.8%) than healthy volunteers (median, 6%; interquartile range, 5.6%-6.3%). These quantitative results confirm what is visually observed on the (3)He images. A Spearman correlation of r = -0.82 was found between the change in whole-lung defect percentage and the number of days between final treatment and second (3)He imaging.Regional quantification of lung ventilation is indeed feasible and may be a useful technique for image-guided treatment of obstructive lung diseases, such as bronchial thermoplasty for severe asthma. In these patients, ventilation defects decreased as a function of time after treatment.

SUBMITTER: Thomen RP

PROVIDER: S-EPMC4314114 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Regional ventilation changes in severe asthma after bronchial thermoplasty with (3)He MR imaging and CT.

Thomen Robert P RP Sheshadri Ajay A Quirk James D JD Kozlowski Jim J Ellison Henry D HD Szczesniak Rhonda D RD Castro Mario M Woods Jason C JC

Radiology 20140819 1

<h4>Purpose</h4>To quantify regional lung ventilation in healthy volunteers and patients with severe asthma (both before and after thermoplasty) by using a combination of helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT), with the intention of developing more effective image-guided treatments for obstructive lung diseases.<h4>Materials and methods</h4>With approval of the local institutional review board, informed consent, and an Investigational New Drug Exemption, si ...[more]

PMID: 25144646

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Project description:PurposeBronchial thermoplasty is approved in many countries worldwide as a non-pharmacological treatment for severe asthma. This review summarizes recent publications on the selection of patients with severe asthma for bronchial thermoplasty, predictors of a beneficial response and developments in the procedure and discusses specific issues about bronchial thermoplasty including effectiveness in clinical practice, mechanism of action, cost-effectiveness, and place in management.ResultsBronchial thermoplasty is a treatment option for patients with severe asthma after assessment and management of causes of difficult-to-control asthma, such as nonadherence, poor inhaler technique, comorbidities, under treatment, and other behavioral factors. Patients treated with bronchial thermoplasty in clinical practice have worse baseline characteristics and comparable clinical outcomes to clinical trial data. Bronchial thermoplasty causes a reduction in airway smooth muscle mass although it is uncertain whether this effect explains its efficacy since other mechanisms of action may be relevant, such as alterations in airway epithelial, gland, and/or nerve function; improvements in small airway function; or a placebo effect. The cost-effectiveness of bronchial thermoplasty is greater in countries where the costs of hospitalization and emergency department are high. The place of bronchial thermoplasty in the management of severe asthma is not certain, although some experts propose that bronchial thermoplasty should be considered for patients with severe asthma associated with non-type 2 inflammation or who fail to respond favorably to biologic therapies targeting type 2 inflammation.ConclusionBronchial thermoplasty is a modestly effective treatment for severe asthma after assessment and management of causes of difficult-to-control asthma. Asthma morbidity increases during and shortly after treatment. Follow-up studies provide reassurance on the long-term safety of the procedure. Uncertainties remain about predictors of response, mechanism(s) of action, and place in management of severe asthma.

Project description:BackgroundBronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response.MethodsIn this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders.ResultsGene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders.ConclusionLocal differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.

Project description:BackgroundBronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma.ObjectiveWe sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy.MethodsBT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans.ResultsOne hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV₁ values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT.ConclusionsThese data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β₂-agonists.

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Regional ventilation changes in severe asthma after bronchial thermoplasty with (3)He MR imaging and CT.

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Regional ventilation changes in severe asthma after bronchial thermoplasty with (3)He MR imaging and CT.

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