medwireNews: Treatment with elexacaftor–tezacaftor–ivacaftor (ETI) reverses cylindrical bronchial dilatations in just 5% of adults with cystic fibrosis (CF), according to a study published in the European Respiratory Journal.
As “most bronchial dilatations found in [adults with] CF cannot be reversed,” the findings contribute to the thinking that cystic fibrosis transmembrane conductance regulators (CFTRs) “should be started earlier in life before the occurrence of irreversible bronchial lesions,” say investigator Pierre-Régis Burgel (Hôpital Cochin, Paris, France) and colleagues.
They reviewed chest computed tomography (CT) scans of 235 adults in France with CF performed up to 9 months prior to initiating ETI and again at least 12 months afterwards. The mean age of the participants was 32.4 years and 53.0% were women.
Bronchial dilatation was considered reversed when the ratio of lumen diameter to the diameter of the adjacent artery was 1 or above before ETI and less than 1 after ETI.
At follow-up CT at a mean of 12.5 months, 12 (5%) participants showed reversal of cylindrical bronchial dilatations.
These 12 patients were then compared with a random sample of 36 patients without reversal of bronchial dilatations. The mean age of the two groups was 31.6 years and 56.0% were men. Just over half (54.0%) were homozygous for the F508del CFTR allele and the mean percent predicted forced expiratory volume in 1 second was 58.8%.
ETI treatment resulted in a significant improvement in the severity of structural abnormalities, with the mean Brody score for the group as a whole decreasing from 79.4 points at baseline to 54.8 points, and significant reductions were seen for bronchial wall thickening, mucus plugging, and parenchymal abnormalities.
Reversal of bronchial dilatations was confirmed in the 12 patients by a significant decrease in bronchial lumen diameter, which prior to ETI was larger among those with than without reversal, at 3.9 mm versus 3.5 mm, but it decreased significantly by 0.7 mm in the former group while increasing significantly by 0.1 mm in the latter group.
This reduction in bronchial lumen diameter among individuals with bronchial dilatation reversal may be associated with the significant mean 6.6% decrease in lung volume seen in these individuals following ETI treatment, compared with a 2.3% increase in those without reversal, say the researchers.
They add that this decrease in lung volume may be indicative of a decrease in lung distension rather than variations in inspiratory levels.
Another possible explanatory factor for reversal is less severe bronchial wall damage, the team speculates. The patients with bronchial dilatation reversal had, on average, a thinner bronchial wall thickness before treatment than those without reversal (1.1 vs 1.2 mm), which meant their ratio of bronchial wall thickness to total bronchial diameter was significantly lower (36.0 vs 39.7 mm). However, mean thickness increased by a significant 3.5 mm with treatment, whereas it decreased by a significant 2.9 mm among those without reversal.
Burgel and co-investigators note that in their study, reversal “was limited to selected cylindrical bronchial dilatations, whereas no reversal was identified in varicose or saccular bronchial dilatations subtypes.”
They surmise that “cylindrical bronchial dilatations are partly related to the consequence of bronchial distension on mildly damaged bronchi rather than to irreversible alteration of the bronchial wall.”
The researchers therefore conclude that as cylindrical bronchial dilatations represent earlier and milder lesions and CF is a progressive disease, “reversal of bronchial dilatations may be more prevalent in children with CF.”
However, they stress that this would need to be explored in further studies.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group