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Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 694-699

Endogenous Airway Acidification
Implications for Asthma Pathophysiology

JOHN F. HUNT, KEZHONG FANG, RAJESH MALIK, ASHLEY SNYDER, NEIL MALHOTRA, THOMAS A. E. PLATTS-MILLS, and BENJAMIN GASTON

Divisions of Pediatric Respiratory Medicine, Pediatric Hematology/Oncology, and Allergy, Asthma and Immunology, University of Virginia Health System, Charlottesville, Virginia

Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivities/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 ± 0.21, n = 22) than in control subjects (7.65 ± 0.20, n = 19, p < 0.001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values, the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology. Hunt JF, Fang K, Malik R, Snyder A, Malhotra N, Platts-Mills TAE, Gaston B. Endogenous airway acidification: implications for asthma pathophysiology.




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Chest, September 1, 2003; 124(3): 1046 - 1052.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Zelenina, A. A. Bondar, S. Zelenin, and A. Aperia
Nickel and Extracellular Acidification Inhibit the Water Permeability of Human Aquaporin-3 in Lung Epithelial Cells
J. Biol. Chem., August 8, 2003; 278(32): 30037 - 30043.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
C. Wijkstrom-Frei, S. El-Chemaly, R. Ali-Rachedi, C. Gerson, M. A. Cobas, R. Forteza, M. Salathe, and G. E. Conner
Lactoperoxidase and Human Airway Host Defense
Am. J. Respir. Cell Mol. Biol., August 1, 2003; 29(2): 206 - 212.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
K. S. van's Gravesande, M. E. Wechsler, H. Grasemann, E. S. Silverman, L. Le, L. J. Palmer, and J. M. Drazen
Association of a Missense Mutation in the NOS3 Gene with Exhaled Nitric Oxide Levels
Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 228 - 231.
[Abstract] [Full Text] [PDF]

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 ChestHome page
E. Baraldi, L. Ghiro, V. Piovan, S. Carraro, G. Ciabattoni, P. J. Barnes, and P. Montuschi
Increased Exhaled 8-Isoprostane in Childhood Asthma
Chest, July 1, 2003; 124(1): 25 - 31.
[Abstract] [Full Text] [PDF]

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 ChestHome page
L. M. Schachter, J. Dixon, R. J. Pierce, and P. O'Brien
Severe Gastroesophageal Reflux Is Associated With Reduced Carbon Monoxide Diffusing Capacity
Chest, June 1, 2003; 123(6): 1932 - 1938.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
E Baraldi, S Carraro, R Alinovi, A Pesci, L Ghiro, A Bodini, G Piacentini, F Zacchello, and S Zanconato
Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations
Thorax, June 1, 2003; 58(6): 505 - 509.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. K. Inglis, S. M. Wilson, and R. E. Olver
Secretion of acid and base equivalents by intact distal airways
Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L855 - L862.
[Abstract] [Full Text] [PDF]

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 Arch. Dis. Child.Home page
E Baraldi, L Ghiro, V Piovan, S Carraro, F Zacchello, and S Zanconato
Safety and success of exhaled breath condensate collection in asthma
Arch. Dis. Child., April 1, 2003; 88(4): 358 - 360.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. Widdicombe, J. F. Hunt, B. Gaston, K. Kostikas, and S. Loukides
"Acidopnea" and the dictionary
Am. J. Respir. Crit. Care Med., March 1, 2003; 167(5): 800 - 801.
[Full Text]

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 Am. J. Respir. Crit. Care Med.Home page
M. Corradi, G. Folesani, R. Andreoli, P. Manini, A. Bodini, G. Piacentini, S. Carraro, S. Zanconato, and E. Baraldi
Aldehydes and Glutathione in Exhaled Breath Condensate of Children with Asthma Exacerbation
Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 395 - 399.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
D. McShane, J.C. Davies, M.G. Davies, A. Bush, D.M. Geddes, and E.W.F.W. Alton
Airway surface pH in subjects with cystic fibrosis
Eur. Respir. J., January 1, 2003; 21(1): 37 - 42.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
R. M. Effros, B. M. Gaston, and J. F. Hunt
Do low exhaled condensate nh4+ concentrations in asthma reflect reduced pulmonary production?
Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 91 - 92.
[Full Text]

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 GutHome page
K Dua, E Bardan, J Ren, Z Sui, and R Shaker
Effect of chronic and acute cigarette smoking on the pharyngoglottal closure reflex
Gut, December 1, 2002; 51(6): 771 - 775.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
S Tate, G MacGregor, M Davis, J A Innes, and A P Greening
Airways in cystic fibrosis are acidified: detection by exhaled breath condensate
Thorax, November 1, 2002; 57(11): 926 - 929.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M. Kollarik and B. J Undem
Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig
J. Physiol., September 1, 2002; 543(2): 591 - 600.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
Members of the Task Force:, E. Baraldi, J.C. de Jongste, B. Gaston, K. Alving, P.J. Barnes, H. Bisgaard, A. Bush, C. Gaultier, H. Grasemann, et al.
Measurement of exhaled nitric oxide in children, 2001: E. Baraldi and J.C. de Jongste on behalf of the Task Force
Eur. Respir. J., July 1, 2002; 20(1): 223 - 237.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
E. Demoncheaux, D. Crowther, A. C. Spivey, T. W. Higenbottam, P. J. Barnes, and S. A. Kharitonov
Monitoring reactive nitrogen species in biological milieu: A difficult journey
Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1670 - 1671.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
B. Gaston and J. F. Hunt
How Acidopneic Is My Patient? A New Question in the Pulmonary Laboratory
Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1349 - 1350.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
K. Kostikas, G. Papatheodorou, K. Ganas, K. Psathakis, P. Panagou, and S. Loukides
pH in Expired Breath Condensate of Patients with Inflammatory Airway Diseases
Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1364 - 1370.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
A. H. Snyder, M. E. McPherson, J. F. Hunt, M. Johnson, J. S. Stamler, and B. Gaston
Acute Effects of Aerosolized S-Nitrosoglutathione in Cystic Fibrosis
Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 922 - 926.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
W. Formanek, D. Inci, R.P. Lauener, J.H. Wildhaber, U. Frey, and G.L. Hall
Elevated nitrite in breath condensates of children with respiratory disease
Eur. Respir. J., March 1, 2002; 19(3): 487 - 491.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
R. W. Hyde
""I Don't Know What You Guys Are Measuring But You Sure Are Measuring It!"" . A Fair Criticism of Measurements of Exhaled Condensates?
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 561 - 562.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
R. M. EFFROS, K. W. HOAGLAND, M. BOSBOUS, D. CASTILLO, B. FOSS, M. DUNNING, M. GARE, W. LIN, and F. SUN
Dilution of Respiratory Solutes in Exhaled Condensates
Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 663 - 669.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Harbord, M. Novelli, B. Canas, D. Power, C. Davis, J. Godovac-Zimmermann, J. Roes, and A. W. Segal
Ym1 Is a Neutrophil Granule Protein That Crystallizes in p47phox-deficient Mice
J. Biol. Chem., February 8, 2002; 277(7): 5468 - 5475.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
O. W. Griffith
Glutaminase and the Control of Airway pH . Yet Another Problem for the Asthmatic Lung?
Am. J. Respir. Crit. Care Med., January 1, 2002; 165(1): 1 - 2.
[Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
L. M. VAN DEN TOORN, S. E. OVERBEEK, J. C. DE JONGSTE, K. LEMAN, H. C. HOOGSTEDEN, and J.-B. PRINS
Airway Inflammation Is Present during Clinical Remission of Atopic Asthma
Am. J. Respir. Crit. Care Med., December 1, 2001; 164(11): 2107 - 2113.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. B. KHATRI, M. OZKAN, K. MCCARTHY, D. LASKOWSKI, J. HAMMEL, R. A. DWEIK, and S. C. ERZURUM
Alterations in Exhaled Gas Profile during Allergen-induced Asthmatic Response
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1844 - 1848.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. J. TOBIN
Asthma, Airway Biology, and Allergic Rhinitis in AJRCCM 2000
Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1559 - 1580.
[Full Text] [PDF]

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 ThoraxHome page
M Silvestri, F Sabatini, D Spallarossa, L Fregonese, E Battistini, M G Biraghi, and G A Rossi
Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthma
Thorax, November 1, 2001; 56(11): 857 - 862.
[Abstract] [Full Text] [PDF]


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