Reviews and feature article
Using imaging as a biomarker for asthma

https://doi.org/10.1016/j.jaci.2016.11.009Get rights and content

There have been significant advancements in the various imaging techniques being used for the evaluation of asthmatic patients, both from a clinical and research perspective. Imaging characteristics can be used to identify specific asthmatic phenotypes and provide a more detailed understanding of endotypes contributing to the pathophysiology of the disease. Computed tomography, magnetic resonance imaging, and positron emission tomography can be used to assess pulmonary structure and function. It has been shown that specific airway and lung density measurements using computed tomography correlate with clinical parameters, including severity of disease and pathology, but also provide unique phenotypes. Hyperpolarized 129Xe and 3He are gases used as contrast media for magnetic resonance imaging that provide measurement of distal lung ventilation reflecting small-airway disease. Positron emission tomography can be useful to identify and target lung inflammation in asthmatic patients. Furthermore, imaging techniques can serve as a potential biomarker and be used to assess response to therapies, including newer biological treatments and bronchial thermoplasty.

Section snippets

Use of imaging in the clinical evaluation of asthma

Imaging of the lungs in asthmatic patients has evolved dramatically over the last decade; however, the clinical diagnosis of asthma is still based on a compatible history, examination findings, and evidence of variable airflow obstruction. Chest imaging is most helpful in evaluating complications from asthma and ruling out alternative diagnoses. The chest radiographic findings are nonspecific and often can be normal. The most common abnormal finding is bronchial wall thickening, which is

Assessing lung structure and function with CT, OCT, EBUS, PET, and MRI

With the drive to more broadly use CT for its newfound roles in clinical assessment of the lung, screening, phenotyping, and drug and device discovery and outcomes assessment, there have been rapid advances, bringing highly evolved CT technologies into the clinical environment. CT imaging can provide comprehensive evaluation of the lung by allowing for detailed descriptions of not only the airway tree and lung parenchyma but also regional ventilation.2 Multidetector row CT allows for faster

Relating structure and function to clinical parameters

Airway remodeling is a term used to describe increased airway WT in asthmatic patients. This condition encompasses a range of processes, including mucous gland hyperplasia, smooth muscle hypertrophy, inflammatory cell infiltration, and collagen deposition.73 CT has been used to evaluate the extent of airway wall thickening.74, 75 WA% and WT percentage (WT%) measured by using CT were increased in patients with severe asthma and correlated with airway epithelial thickness on endobronchial biopsy

Imaging as a biomarker

The effect of inhaled corticosteroid use on air trapping in patients with mild-to-moderate asthma with uncontrolled symptoms has been assessed by using CT. After completing 3 months of therapy with an inhaled corticosteroid, patients exhibited a decrease in air trapping, as measured by using CT.80 Thus air trapping can serve as a potential outcome related to disease control. Recently, biologic therapy with anti–IL-5 mAb has shown promise to reverse the airway remodeling process. In 26 patients

Conclusion

Current use of chest CT in asthmatic patients has been used to identify alternative diagnosis or complicating conditions that might be contributing to uncontrolled disease. Recent studies have now demonstrated that quantitative CT of the chest and hyperpolarized gas MRI can be used as a biomarker of airway remodeling. Prospective longitudinal trials of targeted biologics (anti-IgE, IL-5, IL-4α, and IL-13) and nonpharmacologic (bronchial thermoplasty) treatments using these quantitative imaging

References (82)

  • S.B. Fain et al.

    Evaluation of structure-function relationships in asthma using multidetector CT and hyperpolarized He-3 MRI

    Acad Radiol

    (2008)
  • S. Diaz et al.

    Validity of apparent diffusion coefficient hyperpolarized 3He-MRI using MSCT and pulmonary function tests as references

    Eur J Radiol

    (2009)
  • L. Dougherty et al.

    Use of an optical flow method for the analysis of serial CT lung images

    Acad Radiol

    (2006)
  • J.G. Venegas et al.

    The distribution of ventilation during bronchoconstriction is patchy and bimodal: a PET imaging study

    Respir Physiol Neurobiol

    (2005)
  • J.W. De Backer et al.

    Computational fluid dynamics can detect changes in airway resistance in asthmatics after acute bronchodilation

    J Biomech

    (2008)
  • K.R. Minard et al.

    Phase-contrast MRI and CFD modeling of apparent 3He gas flow in rat pulmonary airways

    J Magn Reson

    (2012)
  • R.L. Walenga et al.

    Current inhalers deliver very small doses to the lower tracheobronchial airways: assessment of healthy and constricted lungs

    J Pharm Sci

    (2016)
  • R. Grimm et al.

    Self-gated MRI motion modeling for respiratory motion compensation in integrated PET/MRI

    Med Image Anal

    (2015)
  • A. Chetta et al.

    Airways remodeling is a distinctive feature of asthma and is related to severity of disease

    Chest

    (1997)
  • J.M. Tunon-de-Lara et al.

    Air trapping in mild and moderate asthma: effect of inhaled corticosteroids

    J Allergy Clin Immunol

    (2007)
  • N. Zha et al.

    Second-order texture measurements of 3He ventilation MRI: proof-of-concept evaluation of asthma bronchodilator response

    Acad Radiol

    (2016)
  • R. Hartley et al.

    Novel imaging approaches in adult asthma and their clinical potential

    Expert Rev Clin Immunol

    (2015)
  • S. Gupta et al.

    Quantitative analysis of high resolution computed tomography scans in severe asthma subphenotypes

    Thorax

    (2010)
  • S. Gupta et al.

    Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients

    J Allergy Clin Immunol

    (2014)
  • R.P. Thomen et al.

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

    Radiology

    (2015)
  • K. Sarikonda et al.

    Predictors of bronchial thermoplasty response in patients with severe refractory asthma

    Am J Resp Crit Care Med

    (2014)
  • D. Lynch et al.

    Uncomplicated asthma in adults: comparison of CT appearance of the lungs in asthmatic healthy subjects

    Radiology

    (1993)
  • F. Paganin et al.

    Chest radiography and high resolution computed tomography of the lungs in asthma

    Am Rev Respir Dis

    (1992)
  • S. Zieverink et al.

    Emergency room radiography of asthma: an efficacy study

    Radiology

    (1982)
  • H. Gono et al.

    Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma

    Eur Respir J

    (2003)
  • E. Harmanci et al.

    High-resolution computed tomography findings are correlated with disease severity in asthma

    Respiration

    (2002)
  • S. Fain et al.

    Imaging of lung function using hyperpolarized helium-3 magnetic resonance imaging: review of current and emerging translational methods and applications

    J Magn Reson Imaging

    (2010)
  • E.A. Hoffman et al.

    Pulmonary CT and MRI phenotypes that help explain chronic pulmonary obstruction disease pathophysiology and outcomes

    J Magn Reson Imaging

    (2016)
  • J.P. Sieren et al.

    SPIROMICS protocol for multicenter quantitative computed tomography to phenotype the lungs

    Am J Respir Crit Care Med

    (2016)
  • C.J. Galbán et al.

    Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression

    Nat Med

    (2012)
  • M. Kirby et al.

    A novel computed tomography disease probability measure (DPM) to phenotype subjects in Cancold

    Am J Respir Crit Care Med

    (2014)
  • M. Kirby et al.

    Sex differences evaluated using computed tomography derived disease probability measure in the population-based CanCOLD Study

    Am J Respir Crit Care Med

    (2015)
  • OECD. Medical technologies. In: Health at a glance 2013: OECD indicators. OECD Publishing. Available at:...
  • IMV 2006 CT market summary report

    (2006)
  • A. Berrington de González et al.

    Projected cancer risks from computed tomographic scans performed in the United States in 2007

    Arch intern Med

    (2009)
  • A.J. Einstein et al.

    Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography

    JAMA

    (2007)
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