Abstract
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, I2 = 42%), amiloride-sensitive (ENaC) (−2.87 mV, 95% CI: −4.02 to −1.72, P < 0.00001, I2 = 51%), and -resistant fractions (−3.91 mV, 95% CI: −7.64 to −0.18, P = 0.04, I2 = 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.
Highlights
Basal NPD was composed of electrogenic transepithelial Na+ and Cl− movement-generated ion gradients
Seven studies were on high altitude pulmonary edema (HAPE)[16,18,19,28,29,30,31], and the other four studies on respiratory distress syndrome (RDS)[25,27,32,33]
Our analyses demonstrate that hypoxia associated with Acute lung injury (ALI) inhibits amiloride-sensitive NPD and stimulates CFTR-associated NPD
Summary
Basal NPD was composed of electrogenic transepithelial Na+ and Cl− movement-generated ion gradients. The correlation of impaired machinery of salt and fluid transport across the alveoli and NPD was documented in several preclinical models[15]. These preclinical studies in gene-manipulating and lung injury models demonstrate a consistent functional alteration between nasal and alveolar transepithelial ion transport, and correlations between ion transport activity and their transcription/translation levels. As the first meta-analysis of the relationship between ion transport activity and severity of ALI, a significant decrease in both total NPD and ENaC fraction was found in HAPE and RDS patients. We conclude that ENaC-associated NPD is more sensitive to hypoxia associated ALI/ARDS than other fractions. A clinical trial will further confirm the O2 sensitivity of ENaC, which may be a proper marker of severity and prognosis of edematous lung injury
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