Pre-COPD has been put forward as potential precursor stage of COPD. We have previously demonstrated that - compared to control - there is a lower number of terminal bronchioles (TB) in pre-COPD. Interalveolar pores are thought to be important to equalize pressure between alveoli, especially in chronic airway obstruction, to prevent retro-obstructive alveolar collapse. However, their morphology and relation to small airway disease in (pre-)COPD is not well understood.

We collected surgical specimens (lobectomy or transplantation) from patients with pre-COPD (n=10), COPD GOLD I (n=6), GOLD II (n=6), GOLD III/IV (n=7), and controls (n=7). MicroCT was performed on tissue samples, for quantification of the number of TB/mL, number of alveolar attachments and surface density. On the same tissue, scanning electron microscopy was performed to quantify the size and number of interalveolar pores on 20 pictures from 2 distinct zones.

There was no difference in the number of pores across the different groups (p=0.83). However, there was an increased pore size in GOLD I (p<.0.05), GOLD II (p<0.05) and GOLD III/IV (p<0.001) compared to control. There was no difference between pre-COPD and control (p=0.28), despite the lower number of TB/mL in pre-COPD. In addition, there was a significant correlation between the size of the pores and TB/mL (p<0.0001, R=-0.59), the number of alveolar attachments (p<0.0001, R=-0.59) and surface density (p<0.0001, R=-0.49).

An increase in the interalveolar pore size, but not pore number is observed with increasing COPD severity. The lack of difference in pore size in pre-COPD can explain why these patients not (yet) present with an obstructive pulmonary function defect.