One major function of the airways is to inactivate and remove pathogens from inhaled air and thereby prevent infection. The secretion of protons by the airway epithelium presents an integral part of the innate host defense mechanism and involves the proton channel (hydrogen voltage-gated channel 1, HVCN1). The purpose of this study was to measure the effect of airway inflammation on acid secretion in asthmatic and non-asthmatic patients with chronic rhinosinusitis by using freshly excised human sinonasal tissue.
Nasal or sinus mucosa from subjects with three different conditions (normal, chronic rhinosinusitis (CRS), CRS with asthma) was harvested during sinus surgery. The rate of proton (H+) secretion by each tissue was measured using the pH-stat titration technique in an Ussing type chamber. The contribution of the HVCN1 proton channel to acid secretion was identified using ZnCl2 as a blocker.
Nasal epithelia isolated from subjects with a diagnosis of both chronic rhinosinusitis (CRS) and asthma had a mucosal equilibrium pH = 6.95 (n = 5), which was significantly lower than the equilibrium pH found in nasal epithelia from normal (n = 5, 7.35 ± 0.21) or from subjects with CRS without asthma (n = 5, 7.33 ± 0.15). When alkalinizing the mucosal pH to 8.0, nasal epithelia from CRS with asthma (n = 5) secreted H+ at a rate of 135.1±46.2 nmol·min−1·cm−2. This rate was significantly higher compared to normal (73.3±39.3 nmol·min−1·cm−2, n = 8) or CRS without asthma (51.4±27.7 nmol·min−1·cm−2, n = 7). Mucosal addition of ZnCl2 blocked H+ secretion by 70% in normal, 52.6% in CRS without asthma, and by 50.8% in CRS with asthma.
Freshly excised human nasal and sinus epithelia secrete acid across the apical cell membrane. Sinonasal tissue isolated from asthmatic CRS patients showed lower mucosal pH values and higher rates of H+ secretion than CRS and normal subjects, and ~50–70% of acid secretion was mediated by the HVCN1 H+ channel in all groups. Excessive acid secretion might contribute to epithelial injury in CRS patients with asthma.