Examples of new or emerging techniques for studying COPD and idiopathic pulmonary fibrosis (IPF)

TechniqueDescriptionUses and advances made with the techniqueCurrent limitations
Micro-CT imagingHigh-resolution CT imaging
  • Higher-resolution versus standard CT imaging [61]

  • Can reveal structural changes associated with small airway disease [61]

  • Reveals massive loss in number and area of terminal bronchioles in patients with centrilobular emphysematous COPD [6]

  • When partnered with parametric response mapping as an imaging biomarker, micro-CT could identify terminal bronchiole pathology in COPD [62]

Performed on ex vivo samples, or explants, rather than on the patient [6, 61, 62]
PETMolecular imaging; most commonly measuring 18F-FDG uptake
  • Has been explored as a noninvasive biomarker for pulmonary inflammation [63]

  • Ability to quantify inflammation is under investigation [63]

Validation of imaging approaches required; changes in lung air, blood and water volumes depending on disease severity can cause variations in signals [63]
Gas diffusion MRINoble gases such as 3He and 129Xe used to visualise lung structure
  • Could be used to monitor disease progression and response to therapy [59]

  • Can detect microstructural changes in the lung, even in asymptomatic smokers [59]

  • Quantitative microstructure data obtainable by measuring gas diffusion in alveoli; the technique can differentiate between patients with COPD and healthy individuals [64]

  • Alveolar sizes can be visualised to form a picture of alveolar loss in COPD [64]

  • Provides sensitive and reproducible data on gas exchange impairment in IPF, correlating with spirometry data [65]

Adaption of existing scanners is required [66]
SPECTRadiotracers used to image the lung, where both airways and blood flow can be imaged
  • Both the airways and blood flow can be imaged, allowing the detection of comorbidities such as pulmonary embolism [67, 68]

  • Can detect abnormalities in apparently healthy smokers [69]

  • Only semi-quantitative [69]

  • Not as high resolution as other imaging methods [68]

  • Takes a long time to acquire an image (e.g. 45 min) [68]

IOSNoninvasive measurement of respiratory mechanics in response to pressure oscillations
  • A reliable tool for investigating proximal and peripheral airways resistance in patients with COPD [70]

  • Peripheral airway resistance and compliance using IOS closely linked to COPD severity and exacerbations [58]

  • Could be used as a screening tool for early-stage COPD [58]

  • Useful for patients who cannot perform spirometry manoeuvres [71]

  • The minimal clinically important difference in IOS parameters needs to be established

OCTA high-resolution optical imaging method
  • Resolution down to micrometre scale [72]

  • Can be used to accurately measure distal airways [73]

  • Could detect early changes to the distal airways and appears to be more sensitive than CT [72, 73]

  • Ultrafine bronchoscopy (with sedation) required to reach the distal airways [73]

Multiple-breath nitrogen washoutNoninvasive measurement of residual nitrogen in the airways to detect any abnormalities in gas distribution in the lung
  • Does not require maximal effort and can be used in a paediatric setting [74]

  • Provides information on abnormalities in the small airways, including terminal bronchioles [75]

  • Can detect abnormalities in early disease [76]

  • Limited standardisation, which impacts the availability of widely applicable reference values [75]

BreathomicsExhaled breath analysis to detect changes in volatile organic compounds
  • Could be used to diagnose COPD and differentiate COPD from asthma [77]

  • May be able to predict disease progression [77]

  • Could help distinguish COPD phenotypes [77]

  • Results can be confounded by parameters such as medication use, comorbidities, smoking and study site [77]

CT: computed tomography; PET: positron emission tomography; 18F-FDG: 18F-2-fluoro-2-deoxy-d-glucose; MRI: magnetic resonance imaging; SPECT: single-photon emission computed tomography; IOS: impulse oscillometry; OCT: optical coherence tomography.