Sputum Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity in Severe Asthma

Svenningsen, Sarah; Eddy, Rachel L.; Lim, Hui Fang; Cox, P. Gerard; Nair, Parameswaran; Párraga, Grace

doi:10.1164/rccm.201709-1948oc

Cited by 75 publications

(74 citation statements)

References 30 publications

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“…These findings are consistent with unresolved small airway abnormalities or mucus plugs (37) leading to persistent ventilation defects that are not reversed by using salbutamol, which mainly has receptors in the central airways. This could be consistent with airway inflammation (18) and suggests that irreversible FEV 1 and worsening ventilation defects may result from inadequate treatment and/or poor adherence to prescribed asthma medication. MRI VDV at baseline predicted bronchodilator reversibility at follow-up whereas age, PC 20 , and FEV 1 did not predict bronchodilator reversibility.…”

Section: Fev 1 and Ventilation Defects Postbronchodilator Reversibilisupporting

confidence: 60%

“…Parametric response map gas trapping was shown (14) to be increased in participants with severe asthma compared with participants with nonsevere asthma and control participants. Inhaled hyperpolarized gas MRI directly probes ventilation as a consequence of both central and peripheral airway function and has revealed the presence of nonrandom ventilation defects (15) that are the functional consequences of airway remodeling, inflammation, and/or intraluminal plugging (16)(17)(18). In patients with asthma, MRI ventilation defects are spatially related to abnormally remodeled airways (16,17), positively correlated with disease severity (19), and improved in response to bronchodilators (15,20).…”

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confidence: 99%

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Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility

et al. 2019

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Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3 He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV 1) reversibility Materials and Methods: Spirometry and hyperpolarized 3 He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre-and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV 1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV 1 at follow-up, and differences between reversible and notreversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV 1 reversibility at follow-up. Results: Eleven participants with asthma (mean age, 42 years 6 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months 6 7. Medications, exacerbations, FEV 1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV 1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV 1 by 20% (PC 20) was greater in FEV 1irreversible participants at follow-up (P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up (R 2 = 0.80; P , .01), but PC 20 , age, and FEV 1 did not (R 2 = 0.63; P = .15). Conclusion: MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months 6 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations.

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Section: Fev 1 and Ventilation Defects Postbronchodilator Reversibilisupporting

confidence: 60%

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confidence: 99%

Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility

et al. 2019

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“…The A X is linked to patient reported outcomes, the FEV 1 and the distribution of air within the lungs as measured by functional imaging. 18,19,107 Oscillometry is an easy, efficient and sensitive means by which to evaluate both asthma and COPD subjects as well as to monitor their response to treatment. Finally, the aim of these symposium proceedings is to convince others to adopt oscillometry into both practice and clinical trials and report their findings.…”

Section: Copd With Emphysemamentioning

confidence: 99%

Applications of oscillometry in clinical research and practice

Lundblad

Siddiqui

Bossé

et al. 2019

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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Oscillometry is gaining in clinical use and while there is an increased interest in the technique, there is paucity in the understanding of its possibilities and limitations. Oscillometry has seen extensive use in research over several decades, but only recently is the technique being adopted in clinical practice; hence, there is a need to educate the novel users. The goal of the mini symposium arranged in San Diego in 2018 was to discuss the principles of oscillometry, showcase some of the recent ongoing research using this technique and to demonstrate how oscillometry may be used in clinical practice. It was concluded that oscillometry has several advantages over spirometry, most notably, with novel data being shown, its sensitivity allowing early detection of small airways disease not possible with spirometry and it can be used in subjects who have difficulties performing forced maneuvers such as preschool children, the elderly and subjects with handicaps. The site of respiratory pathology can be reflected by the various parameters generated by oscillometry and thus help with both disease diagnosis and localization. While the interpretation of oscillometry parameters and translating them into meaningful pathological correlates is still evolving, it is likely that oscillometry will soon be at the forefront of both pulmonary clinical practice and research. R ESUM EL'oscillom etrie est de plus en plus utilis ee en contexte clinique, mais malgr e l'int erêt accru pour cette technique, la compr ehension de ses possibilit es et de ses limites est encore insuffisante. Pendant plusieurs d ecennies, l'oscillom etrie a largement et e utilis ee dans la recherche, mais l'adoption de cette technique dans la pratique clinique est encore r ecente, de sorte qu'il est n ecessaire de former les nouveaux utilisateurs. Le but de ce mini symposium qui s'est tenu a San Diego en 2018 etait de discuter des principes de l'oscillom etrie, de pr esenter les plus r ecentes etudes utilisant cette technique et de d emontrer comment elle peutêtre utilis ee dans la pratique clinique. Il a et e d etermin e que l'oscillom etrie pr esentait plusieurs avantages par rapport a la spirom etrie notamment, comme le d emontrent de nouvelles donn ees, sa sensibilit e qui permet la d etection pr ecoce de la maladie des petites voies a eriennes, ce que la spirom etrie ne peut pas faire, ainsi que le fait qu'elle puisseêtre utilis ee aupr es de sujets qui eprouvent de la difficult e a effectuer des manoeuvres forc ees comme les enfants d'âge pr escolaire, les personnesâg ees et les personnes atteintes d'un handicap. L'emplacement de la pathologie respiratoire peut se refl eter dans les divers param etres produits par la spirom etrie, ce qui peut contribuer a diagnostiquer la maladie et a la localiser. Bien que l'interpr etation des param etres de l'oscillom etrie et leur traduction dans des corr elats pathologiques significatifs continue d' evoluer, l'oscillom etrie sera vraisemblablement a l'avant-plan de la pratique clinique et de la recherche pulmonair...

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“…An alternative hypothesis is that remodelling and inflammation are distributed unevenly throughout the lung, which allows the worst-affected airways to form ventilation defects. There has been a large body of work on ventilation imaging using hyperpolarised 3 He MRI in asthma [38,82,85,[97][98][99]. The presence of ventilation defects due to airway closure during bronchoconstriction is a consistent finding and recently has been correlated with thickening of the airways measured from CT [99] scans, airway hyperresponsiveness [99] and with eosinophilic inflammation measured in sputum [98] and neutrophilic inflammation [100] measured from bronchoscopic washes.…”

mentioning

confidence: 99%

“…Moreover, there is good evidence from MRI studies that the severity of airway closure, measured by how much lung is not ventilated, is associated with clinical markers of asthma severity [97] and risk of asthma exacerbations [101]. In subjects with severe asthma, ventilation defect volumes reduce with acute bronchodilator inhalation [98], but less so when there is sputum eosinophilia. Therefore, airway closure on ventilation imaging appears to be associated with asthma severity and poor control of type II inflammation and as such, there is a strong argument that ventilation imaging is a clinically relevant physiological measurement for characterising asthma.…”

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confidence: 99%

Dismantling the pathophysiology of asthma using imaging

2019

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Asthma remains an important disease worldwide, causing high burden to patients and healthcare systems and presenting a need for better management and ultimately prevention and cure. Asthma is a very heterogeneous condition, with many different pathophysiological processes. Better measurement of those pathophysiological processes are needed to better phenotype disease, and to go beyond the current, highly limited measurements that are currently used: spirometry and symptoms. Sophisticated three-dimensional lung imaging using computed tomography and ventilation imaging (single photon emission computed tomography and positron emission tomography) and magnetic resonance imaging and methods of lung imaging applicable to asthma research are now highly developed. The body of current evidence suggests that abnormalities in structure and ventilatory function measured by imaging are clinically relevant, given their associations with disease severity, exacerbation risk and airflow obstruction. Therefore, lung imaging is ready for more widespread use in clinical trials and to become part of routine clinical assessment of asthma.

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Sputum Eosinophilia and Magnetic Resonance Imaging Ventilation Heterogeneity in Severe Asthma

Cited by 75 publications

References 30 publications

Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility

Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility

Applications of oscillometry in clinical research and practice

Dismantling the pathophysiology of asthma using imaging

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