Clinical trials of gene therapy for cystic fibrosis (CF) are reaching the stage of intrapulmonary gene delivery. To assess the efficacy of this a technique to measure lower airway potential difference (PD) would be useful. We have, therefore, studied the baseline PD and responses to sequential perfusion with a low chloride solution, amiloride (100 μM), isoprenaline (100 μM) and ATP (100 μM) in non-CF (n=13) and CF (n=6, all ΔF508, FEV1>70% predicted) subjects. Recordings were made under general anaesthesia to avoid the effects of lignocaine. For baseline PD measurements were made at 12 sites (trachea x4), (main bronchus x4), main, segmental, subsegmental airways and a 'wedge' recording. Drug perfusion was undertaken at 2 sites (segmental and tracheal, in that sequence) in each subject. Baseline PD was more negative at all sites in the CF subjects: trachea: non-CF -8.2 mV (1.1), CF -16.1 mV (2.3), main non-CF -7.4 (1.2), CF -17.7 mV (3.0), lobar non-CF -5.4 mV (1.0), CF -21.1 mV (4.9), segmental non-CF -5.8 mV (1.0), CF -18.1 mV (4.4), subsegmental -6.7 mV (0.6), CF -11.3 mV (2.3), wedge non-CF -4.5 mV (0.8), CF -7.7 mV (2.1). Regions of high (more negative) PD were patchy in the CF subjects with maximum values for each region of: trachea -34.3, main -38.5, lobar -39.7, segmental -30.0, subsegmental -24.0, wedge -14.0. Perfusion with a low chloride solution clearly distinguished the two genotypes in the segmental airways (non CF +13.7 mV (3.5), CF -7.4 mV (1.9)) and the trachea (non CF +3.4 mV (0.5), CF -3.7 mV (1.5). Similarly the response to amiloride was increased in the CF subjects: segmental (non-CF 28.6% (9.4), CF 69.3% (8.9)) trachea (non-CF 31.4% (7.9), CF 53.0% (11.2)). The responses to isoprenaline were abolished in the CF subjects: segmental (non-CF +4.4 mV (1.5), CF 0.0 mV (0.0)) trachea (non-CF +2.3 mV (1.0), CF 0.2 mV (0.2)). Responses to ATP were variable and small in non-CF but more readily seen in the CF subjects. We conclude that the lower airways of CF subjects demonstrate many of the electrophysiological features documented for the nasal epithelium, suggesting that these measurements may be useful for the assessment of gene transfer.
|Issue number||SUPPL. 3|
|Publication status||Published - Dec 1996|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine