Journal article
Repurposing tromethamine as inhaled therapy to treat CF airway disease
JCI insight, Vol.1(8), e87535
06/02/2016
DOI: 10.1172/jci.insight.87535
PMCID: PMC4933331
PMID: 27390778
Abstract
In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO
and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO
increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO
-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease.
Details
- Title: Subtitle
- Repurposing tromethamine as inhaled therapy to treat CF airway disease
- Creators
- Mahmoud H Abou Alaiwa - Department of Internal Medicine, Roy J. and Lucille A. Carver College of MedicineJanice L Launspach - Department of Internal Medicine, Roy J. and Lucille A. Carver College of MedicineKelsey A Sheets - Department of Internal Medicine, Roy J. and Lucille A. Carver College of MedicineJade A Rivera - Department of Internal Medicine, Roy J. and Lucille A. Carver College of MedicineNicholas D Gansemer - Department of Internal Medicine, Roy J. and Lucille A. Carver College of MedicinePeter J Taft - Department of Internal Medicine, Roy J. and Lucille A. Carver College of MedicinePeter S Thorne - Department of Occupational and Environmental Health, College of Public HealthMichael J Welsh - Pappajohn Biomedical Institute, andDavid A Stoltz - Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAJoseph Zabner - Pappajohn Biomedical Institute, and
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.1(8), e87535
- Publisher
- United States
- DOI
- 10.1172/jci.insight.87535
- PMID
- 27390778
- PMCID
- PMC4933331
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Grant note
- P30 ES005605 / NIEHS NIH HHS P30 DK054759 / NIDDK NIH HHS P01 HL091842 / NHLBI NIH HHS
- Language
- English
- Date published
- 06/02/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Civil and Environmental Engineering; Occupational and Environmental Health; Neurosurgery; Internal Medicine
- Record Identifier
- 9983997324502771
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