Tracheal aspirate pH is alkaline in pre-term human infants

Paget-Brown, Alix; Hunt, J.F.; Gaston, Benjamin

doi:10.1183/09031936.00015507

Cited by 8 publications

(3 citation statements)

References 9 publications

(17 reference statements)

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“…Our current data suggest that at ASL pH 6.9, acid secretion is low and the H + channel is likely closed. However, ASL pH has been found to alkalinize to values >7 (Fischer and Widdicombe, 2006), and extremes of >8 have been measured under certain conditions (England et al, 1999; Paget-Brown et al, 2007). Although the reason for an excessive alkalinization of the airways is not fully understood, it may be governed by CFTR-mediated HCO 3 − secretion into the ASL (Ballard et al, 1999; Thiagarajah et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T

Iovannisci¹,

Illek²,

Fischer³

2010

Journal of General Physiology

108

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Airways secrete considerable amounts of acid. In this study, we investigated the identity and the pH-dependent function of the apical H+ channel in the airway epithelium. In pH stat recordings of confluent JME airway epithelia in Ussing chambers, Zn-sensitive acid secretion was activated at a mucosal threshold pH of ∼7, above which it increased pH-dependently at a rate of 339 ± 34 nmol × h−1 × cm−2 per pH unit. Similarly, H+ currents measured in JME cells in patch clamp recordings were readily blocked by Zn and activated by an alkaline outside pH. Small interfering RNA–mediated knockdown of HVCN1 mRNA expression in JME cells resulted in a loss of H+ currents in patch clamp recordings. Cloning of the open reading frame of HVCN1 from primary human airway epithelia resulted in a wild-type clone and a clone characterized by two sequential base exchanges (452T>C and 453G>A) resulting in a novel missense mutation, M91T HVCN1. Out of 95 human genomic DNA samples that were tested, we found one HVCN1 allele that was heterozygous for the M91T mutation. The activation of acid secretion in epithelia that natively expressed M91T HVCN1 required ∼0.5 pH units more alkaline mucosal pH values compared with wild-type epithelia. Similarly, activation of H+ currents across recombinantly expressed M91T HVCN1 required significantly larger pH gradients compared with wild-type HVCN1. This study provides both functional and molecular indications that the HVCN1 H+ channel mediates pH-regulated acid secretion by the airway epithelium. These data indicate that apical HVCN1 represents a mechanism to acidify an alkaline airway surface liquid.

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Section: Discussionmentioning

confidence: 99%

Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T

Iovannisci¹,

Illek²,

Fischer³

2010

Journal of General Physiology

108

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“…In a study of exhaled breath condensate, normal average pH was 7.65, which dropped in asthmatics to an average of pH 5.23, and extreme values of pH 4.5 to pH 8.5 were reported (49). In another study, the pH of the tracheal aspirate from neonates was found to be alkaline, ranging between 5.8 and 8.8 (50) and with average pH of 7.8. Bronchoalveolar lavage fluid sampled from neonates is on average acidic with a pH of 5.5 but ranges up to pH 7.5 during respiratory distress (51).…”

Section: Ph Gradientsmentioning

confidence: 96%

Function of proton channels in lung epithelia

Fischer¹

2011

WIREs Membr Transp Signal

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The properties of the voltage-dependent H+ channel have been studied in lung epithelial cells for many years, and recently HVCN1 mRNA expression has been linked directly to H+ channel function in lung epithelium. The H+ channel is activated by strong membrane depolarization, intracellular acidity, or extracellular alkalinity. Early on it was noted that these are surprising physiological channel characteristics when considering that lung epithelial cells have rather stable membrane potentials and a well pH-buffered intracellular milieu. This raised the question under which conditions the H+ channel is active in lung epithelium and what is its physiological function there. Current understanding of the HVCN1 H+ channel in lung epithelial acid secretion, its activation by an alkaline mucosal extracellular pH, and its role in the regulation of the mucosal pH of the lung has resulted in a model of mucosal pH regulation based on the parallel function of the HVCN1 H+ channel and the CFTR HCO3- channel, which suggests that HVCN1 is a critical factor that maintains a neutral surface pH in the lung.

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“…Over the past 15 years, acidification of EBC pH has been studied as a biomarker in a variety of diseases including asthma, [6,16,17] cystic fibrosis, [18,19] respiratory syncytial virus, [14] bronchpulmonary dysplasia, [20] and ARDS [21,22]. It is possible that the ability of the airway epithelium to acidify in response to various insults can be reflected through EBC pH [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

The effects of lung recruitment maneuvers on exhaled breath condensate pH

et al. 2015

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Exhaled breath condensate (EBC) pH serves as a surrogate marker of airway lining fluid (ALF) pH and can be used to evaluate airway acidification (AA). AA is known to be present in acute respiratory distress syndrome (ARDS) and can be evaluated via continuous EBC pH measurement during mechanical ventilation. Lung recruitment maneuvers (LRMs) are utilized in the treatment of ARDS, however, their impact on EBC pH has never been explored. Here we described the acute effects of two commonly used LRMs on EBC pH. In a prospective, non-randomized, serial exposure study, 10 intubated pediatric subjects with acute respiratory distress syndrome sequentially underwent: a period of baseline ventilation, sustained inflation (SI) maneuver of 40 cm H2O for 40 s, open lung ventilation, staircase recruitment strategy (SRS) (which involves a systematic ramping of plateau pressures in 5 cm H2O increments, starting at 30 cm H2O), and PEEP titration. Maximum lung recruitment during the SRS is defined as a PaO2 + PaCO2 of >400 mmHg. Following lung recruitment, PEEP titration was conducted from 20 cm H2O in 2 cm H2O decrements until a PaO2 + PaCO2 was <380 and then increased by 2 cm H2O. EBC pH, arterial blood gases, lung mechanics, hemodynamics, and function residual capacity were obtained following each phase of the LRM and observational period. Seven out of 10 patients were able to reach maximum lung recruitment. Baseline EBC pH (6.38 ± 0.37) did not correlate with disease severity defined by PaO2/FiO2 ratio or oxygenation index (OI). Average EBC pH differed between phases and decreased after LRM (p = 0.001). EBC pH is affected by LRMs. EBC acidification following LRMs may represent a washout effect of opening acidic lung units and ventilating them or acute AA resulting from LRM.

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Tracheal aspirate pH is alkaline in pre-term human infants

Cited by 8 publications

References 9 publications

Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T

Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T

Function of proton channels in lung epithelia

The effects of lung recruitment maneuvers on exhaled breath condensate pH

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