Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury

Nasal potential difference (NPD), a well-established in vivo clinical test for cystic fibrosis, reflects transepithelial cation and anion transport in the respiratory epithelium. To analyze whether NPD can be applied to diagnose hypoxic lung injury, we searched PubMed, EMBASE, Scopus, Web of Science, Ovid MEDLINE, and Google Scholar, and analyzed data retrieved from eleven unbiased studies for high altitude pulmonary edema (HAPE) and respiratory distress syndrome (RDS) using the software RevMan and R. There was a significant reduction in overall basal (WMD -5.27 mV, 95% CI: -6.03 to -4.52, P < 0.00001, I(2) = 42%), amiloride-sensitive (ENaC) (-2.87 mV, 95% CI: -4.02 to -1.72, P < 0.00001, I(2) = 51%), and -resistant fractions (-3.91 mV, 95% CI: -7.64 to -0.18, P = 0.04, I(2) = 95%) in lung injury patients. Further analysis of HAPE and RDS separately corroborated these observations. Moreover, SpO2 correlated with ENaC-associated NPD positively in patients only, but apparently related to CFTR-contributed NPD level inversely. These correlations were confirmed by the opposite associations between NPD values and altitude, which had a negative regression with SpO2 level. Basal NPD was significantly associated with amiloride-resistant but not ENaC fraction. Our analyses demonstrate that acute lung injury associated with systemic hypoxia is characterized by dysfunctional NPD.