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Characterization of acinar airspace involvement in asthmatic patients by using inert gas washout and hyperpolarized 3helium magnetic resonance - 05/02/16

Doi : 10.1016/j.jaci.2015.06.027 
Sherif Gonem, PhD a, Steven Hardy, MPhys b, Niels Buhl, PhD b, Ruth Hartley, MB, ChB a, Marcia Soares, BSc a, Richard Kay, PhD c, Rino Costanza, PhD d, Per Gustafsson, PhD e, Christopher E. Brightling, PhD a, John Owers-Bradley, PhD b, Salman Siddiqui, PhD a,
a Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom 
b Department of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom 
c Novartis Pharmaceuticals, Basel, Switzerland 
d Chiesi UK, Cheadle, United Kingdom 
e Department of Paediatrics, Central Hospital, Skövde, Sweden 

Corresponding author: Salman Siddiqui, PhD, NIHR Respiratory Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester LE3 9QP, United Kingdom.

Abstract

Background

The multiple-breath inert gas washout parameter acinar ventilation heterogeneity (Sacin) is thought to be a marker of acinar airway involvement but has not been validated by using quantitative imaging techniques in asthmatic patients.

Objective

We aimed to use hyperpolarized 3He diffusion magnetic resonance at multiple diffusion timescales and quantitative computed tomographic (CT) densitometry to determine the nature of acinar airway involvement in asthmatic patients.

Methods

Thirty-seven patients with asthma and 17 age-matched healthy control subjects underwent spirometry, body plethysmography, multiple-breath inert gas washout (with the tracer gas sulfur hexafluoride), and hyperpolarized 3He diffusion magnetic resonance. A subset of asthmatic patients (n = 27) underwent quantitative CT densitometry.

Results

Ninety-four percent (16/17) of patients with an increased Sacin had Global Initiative for Asthma treatment step 4 to 5 asthma, and 13 of 17 had refractory disease. The apparent diffusion coefficient (ADC) of 3He at 1 second was significantly higher in patients with Sacin-high asthma compared with that in healthy control subjects (0.024 vs 0.017, P < .05). Sacin correlated strongly with ADCs at 1 second (R = 0.65, P < .001) but weakly with ADCs at 13 ms (R = 0.38, P < .05). ADCs at both 13 ms and 1 second correlated strongly with the mean lung density expiratory/inspiratory ratio, a CT marker of expiratory air trapping (R = 0.77, P < .0001 for ADCs at 13 ms; R = 0.72, P < .001 for ADCs at 1 second).

Conclusion

Sacin is associated with alterations in long-range diffusion within the acinar airways and gas trapping. The precise anatomic nature and mechanistic role in patients with severe asthma requires further evaluation.

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Key words : Asthma, small airways, acinus, physiology

Abbreviations used : ACQ, ADC, CDI, CT, DCDI, FRC, GINA, 3He-MR, ICS, Kco, MBW, MLD E/I, OCS, P15, RV, Sacin, Scond, SF6


Plan


 This article presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health. This work was partly funded through research collaborations with Chiesi Farmaceutici S. P. A. and Novartis Pharmaceuticals. Additional funding was received from the Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) project (funded through an FP7 European Union grant).
 Disclosure of potential conflict of interest: S. Gonem has received travel support from GlaxoSmithKline and Chiesi. R. Kay is employed by Novartis Pharmaceuticals AG. C. E. Brightling has received research support and personal fees from GlaxoSmithKline, MedImmune, Novartis, Roche, Chiesi, and Boehringer Ingelheim. S. Siddiqui has received research support from Chiesi, European Union FP7 (Scheme: AirPROM-FP7), NAPP Pharmaceuticals, and the Sir Jules Thorne Trust and has received lecture fees from the European Respiratory Society and Chiesi. The rest of the authors declare that they have no relevant conflicts of interest.


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Vol 137 - N° 2

P. 417-425 - février 2016 Retour au numéro
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