Imaging of airway remodeling
The direct assessment of human airway remodeling can be performedin vivo on bronchial biopsies in asthmatic patients57, 189, 193. Bronchial biopsies identify useful information on bronchial and pulmonary alterations, such as thickening of the bronchial tissue, infiltration and density of inflammatory cells, aberrant accumulation of elements of ECM, and ASM hyperplasia and hypertrophy 15. However, this procedure has several limitations that should be pointed out. First, it is not part of the routine clinical evaluation of asthmatic patients. Second, it does not easily facilitate serial biopsies in the same patient. Third, the results can be significantly influenced by the operator and the techniques used to assess tissue remodeling.
During the last decade, high-resolution computed tomography (HRCT) and nuclear magnetic resonance (NHR) are gaining a place as non-invasive techniques to examine different aspects of airway remodeling in asthma. Hoshino found increased airway wall thickening in asthmatics assessed by HRTC 194. Endobronchial ultrasound (EBUS) was higher in asthma patients than healthy controls 195. Hartley et al. found that the proximal airway wall area was increased in asthmatics compared to controls196. The loss of the peripheral pulmonary vasculature, also termed pruning, was associated with asthma severity197. Recently, Eddy and co-workers demonstrated that the total number of CT-visible airways was correlated to asthma severity198.
Preliminary results derive from imaging studies that have evaluated the effects of biological therapies on airway remodeling using HRCT. Hoshinoet al. reported that 16-week of treatment with omalizumab reduced the airway wall thickness and the number of sputum eosinophils136. In another study, 48-week treatment with omalizumab reduced the airway wall area corrected for body surface, but no changes in percentage wall area, without changes in the luminal area199. In two studies conducted by Haldar et al.200, 201 on airway remodeling by HRCT, it was found that the biological treatment determined a greater variation in pre/post treatment luminal area when compared to the placebo group. A recent study evaluated the impact of one-year mepolizumab therapy on airway remodeling through EBUS and HRTC. Improved airway remodeling (e.g., reduction in bronchial wall thickness) was better noticeable in invasive EBUS than in non-invasive HRCT202. In the phase 2 CASCADE study, tezepelumab increased the CT scan-determined lumen area across airway generations189.
Hyperpolarized helium-3 MRI of the lung has demonstrated regional heterogeneity of lobar ventilation in asthma203, which is correlated with asthma severity204. MRI ventilation defects (VDP) are correlated to sputum eosinophilia in severe asthma205 and are a predictor of exacerbation206. Collectively, studies with CT and MRI in asthma have shown some structural and functional changes in airways and pulmonary vasculature associated with more severe disease but are unable to differentiate between reversible and potentially irreversible changes.
Finally, fractional exhaled nitric oxide (FeNO) has been proposed to assess airway structure variations in asthma patients, especially in the distal airway. FeNO was associated with bronchial wall thickening in the third to the sixth generation of bronchial trees207.