title: Characterization of acinar airspace involvement in asthmatic patients by using inert gas washout and hyperpolarized (3)helium magnetic resonance.
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 (3)He 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 (3)He 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 (3)He 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Sherif
authors.initials: S
authors.lastname: Gonem
authors.affiliation: Department of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Hardy
authors.affiliation: Department of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Niels
authors.initials: N
authors.lastname: Buhl
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hartley
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Marcia
authors.initials: M
authors.lastname: Soares
authors.affiliation: Novartis Pharmaceuticals, Basel, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Kay
authors.affiliation: Chiesi UK, Cheadle, United Kingdom.
authors.forename: Rino
authors.initials: R
authors.lastname: Costanza
authors.affiliation: Department of Paediatrics, Central Hospital, Skövde, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Gustafsson
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.affiliation: Department of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Owers-Bradley
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom. Electronic address: ss338@le.ac.uk.
authors.forename: Salman
authors.initials: S
authors.lastname: Siddiqui
mesh_terms: D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006371:Helium; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010641:Phenotype; D012129:Respiratory Function Tests / Q000379:methods; D012307:Risk Factors
chemical_list: D006371:Helium
keywords: Asthma; acinus; physiology; small airways