Mahmoud H Abou Alaiwa1, Alison M Beer1, Alejandro A Pezzulo1, Janice L Launspach1, Rebecca A Horan1, David A Stoltz1, Timothy D Starner2, Michael J Welsh3, Joseph Zabner4. 1. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. 2. Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. 3. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: michael-welsh@uiowa.edu. 4. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: joseph-zabner@uiowa.edu.
Abstract
BACKGROUND: Disrupted HCO3(-) transport and reduced airway surface liquid (ASL) pH in cystic fibrosis (CF) may initiate airway disease. We hypothesized that ASL pH is reduced in neonates with CF. METHODS: In neonates with and without CF, we measured pH of nasal ASL. We also measured nasal pH in older children and adults. RESULTS: In neonates with CF, nasal ASL (pH5.2 ± 0.3) was more acidic than in non-CF neonates (pH6.4 ± 0.2). In contrast, nasal pH of CF children and adults was similar to values measured in people without CF. CONCLUSIONS: At an age when infection, inflammation and airway wall remodeling are minimal, neonates with CF had an acidic nasal ASL compared to babies without CF. The CF:non-CF pH difference disappeared in older individuals, perhaps because secondary manifestations of disease increase ASL pH. These results aid understanding of CF pathogenesis and suggest opportunities for therapeutic intervention and monitoring of disease.
BACKGROUND: Disrupted HCO3(-) transport and reduced airway surface liquid (ASL) pH in cystic fibrosis (CF) may initiate airway disease. We hypothesized that ASL pH is reduced in neonates with CF. METHODS: In neonates with and without CF, we measured pH of nasal ASL. We also measured nasal pH in older children and adults. RESULTS: In neonates with CF, nasal ASL (pH5.2 ± 0.3) was more acidic than in non-CF neonates (pH6.4 ± 0.2). In contrast, nasal pH of CF children and adults was similar to values measured in people without CF. CONCLUSIONS: At an age when infection, inflammation and airway wall remodeling are minimal, neonates with CF had an acidic nasal ASL compared to babies without CF. The CF:non-CF pH difference disappeared in older individuals, perhaps because secondary manifestations of disease increase ASL pH. These results aid understanding of CF pathogenesis and suggest opportunities for therapeutic intervention and monitoring of disease.
Authors: Raymond D Coakley; Barbara R Grubb; Anthony M Paradiso; John T Gatzy; Larry G Johnson; Sylvia M Kreda; Wanda K O'Neal; Richard C Boucher Journal: Proc Natl Acad Sci U S A Date: 2003-12-10 Impact factor: 11.205
Authors: Charlotte M H H T Robroeks; Philippe P R Rosias; Dillys van Vliet; Quirijn Jöbsis; Jan-Bart L Yntema; Hein J L Brackel; Jan G M C Damoiseaux; Gertjan M den Hartog; Will K W H Wodzig; Edward Dompeling Journal: Pediatr Allergy Immunol Date: 2008-02-27 Impact factor: 6.377
Authors: David A Stoltz; David K Meyerholz; Alejandro A Pezzulo; Shyam Ramachandran; Mark P Rogan; Greg J Davis; Robert A Hanfland; Chris Wohlford-Lenane; Cassie L Dohrn; Jennifer A Bartlett; George A Nelson; Eugene H Chang; Peter J Taft; Paula S Ludwig; Mira Estin; Emma E Hornick; Janice L Launspach; Melissa Samuel; Tatiana Rokhlina; Philip H Karp; Lynda S Ostedgaard; Aliye Uc; Timothy D Starner; Alexander R Horswill; Kim A Brogden; Randall S Prather; Sandra S Richter; Joel Shilyansky; Paul B McCray; Joseph Zabner; Michael J Welsh Journal: Sci Transl Med Date: 2010-04-28 Impact factor: 17.956
Authors: Lakshmi Durairaj; Janice Launspach; Janet L Watt; Thomas R Businga; Joel N Kline; Peter S Thorne; Joseph Zabner Journal: Respir Res Date: 2004-09-16
Authors: Eugene H Chang; Xiao Xiao Tang; Viral S Shah; Janice L Launspach; Sarah E Ernst; Brieanna Hilkin; Philip H Karp; Mahmoud H Abou Alaiwa; Scott M Graham; Douglas B Hornick; Michael J Welsh; David A Stoltz; Joseph Zabner Journal: Int Forum Allergy Rhinol Date: 2014-10-31 Impact factor: 3.858
Authors: Mahmoud H Abou Alaiwa; Janice L Launspach; Kelsey A Sheets; Jade A Rivera; Nicholas D Gansemer; Peter J Taft; Peter S Thorne; Michael J Welsh; David A Stoltz; Joseph Zabner Journal: JCI Insight Date: 2016-06-02
Authors: Yan Shin J Liao; Shin Ping Kuan; Maria V Guevara; Emily N Collins; Kalina R Atanasova; Joshua S Dadural; Kevin Vogt; Veronica Schurmann; Laura Bravo; Eda Eken; Mariana Sponchiado; Leah R Reznikov Journal: Am J Physiol Lung Cell Mol Physiol Date: 2020-03-11 Impact factor: 5.464
Authors: Susan E Birket; Kengyeh K Chu; Linbo Liu; Grace H Houser; Bradford J Diephuis; Eric J Wilsterman; Gregory Dierksen; Marina Mazur; Suresh Shastry; Yao Li; John D Watson; Alexander T Smith; Benjamin S Schuster; Justin Hanes; William E Grizzle; Eric J Sorscher; Guillermo J Tearney; Steven M Rowe Journal: Am J Respir Crit Care Med Date: 2014-08-15 Impact factor: 21.405
Authors: Pankaj B Agrawal; Ruobing Wang; Hongmei Lisa Li; Klaus Schmitz-Abe; Chantelle Simone-Roach; Jingxin Chen; Jiahai Shi; Tin Louie; Shaohu Sheng; Meghan C Towne; Christine F Brainson; Michael A Matthay; Carla F Kim; Michael Bamshad; Mary J Emond; Norma P Gerard; Thomas R Kleyman; Craig Gerard Journal: Am J Respir Cell Mol Biol Date: 2017-12 Impact factor: 6.914
Authors: Ryan J Adam; Katherine B Hisert; Jonathan D Dodd; Brenda Grogan; Janice L Launspach; Janel K Barnes; Charles G Gallagher; Jered P Sieren; Thomas J Gross; Anthony J Fischer; Joseph E Cavanaugh; Eric A Hoffman; Pradeep K Singh; Michael J Welsh; Edward F McKone; David A Stoltz Journal: JCI Insight Date: 2016-04-07