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Airway acidification: Interactions with nitrogen oxides and airway inflammation

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Abstract

Airway acidification is increasingly appreciated to occur in inflammatory obstructive airway diseases, resulting from acid re.ux and aspiration and from direct acid formation in the airways. Acidity activates oxidants and nitrogen oxides to create a potent antimicrobial environment. Neurogenic inflammation is triggered by airway or esophageal acidi.cation, innate immune cells are affected by acidity, and there are pathways by which the acquired immune system also can be activated by the chemistry of an acidic airway. Measuring airway acidity is now readily achievable with noninvasive breath assays, a procedure that has opened a window on the need to understand airway pH homeostasis in health and pH dysregulation in disease.

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References and Recommended Reading

  1. Bosse GM: Nebulized sodium bicarbonate in the treatment of chlorine gas inhalation. J Toxicol Clin Toxicol 1994, 32:233–241.

    Article  PubMed  CAS  Google Scholar 

  2. Harding SM: Gastroesophageal re.ux: a potential asthma trigger. Immunol Allergy Clin North Am 2005, 25:131–148.

    Article  PubMed  Google Scholar 

  3. Fischer H, Widdicombe JH, Illek B: Acid secretion and proton conductance in human airway epithelium. Am J Physiol Cell Physiol 2002, 282:C736-C743.

    PubMed  CAS  Google Scholar 

  4. Schwarzer C, Machen TE, Widdicombe JH, et al.: Expression of NADPH oxidase homologs and proton secretion in human airway epithelia (abstract). FASEB J 2003, 17:A819.

    Google Scholar 

  5. Wadsworth SJ, Spitzer AR, Chander A: Ionic regulation of proton chemical (pH) and electrical gradients in lung lamellar bodies. Am J Physiol 1997, 273(2 Pt 1):L427-L436.

    PubMed  CAS  Google Scholar 

  6. Kurashima K, Numata M, Yachie A, et al.: The role of vacuolar H(+)-ATPase in the control of intragranular pH and exocytosis in eosinophils. Lab Invest 1996, 75:689–698.

    PubMed  CAS  Google Scholar 

  7. Jabado N, Jankowski A, Dougaparsad S, et al.: Natural resistance to intracellular infections: natural resistanceassociated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 2000, 192:1237–1248.

    Article  PubMed  CAS  Google Scholar 

  8. Burkhardt JK, Hester S, Lapham CK, Argon Y: The lytic granules of natural killer cells are dual-function organelles combining secretory and pre-lysosomal compartments. J Cell Biol 1990, 111(6 Pt 1):2327–2340.

    Article  PubMed  CAS  Google Scholar 

  9. Tapper H, Sundler R: Cytosolic pH regulation in mouse macrophages: proton extrusion by plasma-membrane-localized H(+)-ATPase. Biochem J 1992, 281(Pt 1):245–250.

    PubMed  CAS  Google Scholar 

  10. Ricciardolo FL, Gaston B, Hunt J: Acid stress in the pathology of asthma. J Allergy Clin Immunol 2004, 113:610–619. Overview of airway acid stress and neurogenic inflammation, with clear summary images.

    Article  PubMed  CAS  Google Scholar 

  11. Holma B: In.uence of buffer capacity and pH-dependent rheological properties of respiratory mucus on health effects due to acidic pollution. Sci Total Environ 1985, 41:101–123.

    Article  PubMed  CAS  Google Scholar 

  12. Holma B, Lindegren M, Andersen JM: pH effects on ciliomotility and morphology of respiratory mucosa. Arch Environ Health 1977, 32:216–226.

    PubMed  CAS  Google Scholar 

  13. Clary-Meinesz C, Mouroux J, Cosson J, et al.: In.uence of external pH on ciliary beat frequency in human bronchi and bronchioles. Eur Respir J 1998, 11:330–333.

    Article  PubMed  CAS  Google Scholar 

  14. Trevani AS, Andonegui G, Giordano M, et al.: Extracellular acidi.cation induces human neutrophil activation. J Immunol 1999, 162:4849–4857.

    PubMed  CAS  Google Scholar 

  15. Rabinovich M, DeStefano MJ, Dziezanowski MA: Neutrophil migration under agarose: stimulation by lowered medium pH and osmolality. J Reticuloendothel Soc 1980, 27:189–200.

    PubMed  CAS  Google Scholar 

  16. Hunt JF, Fang K, Malik R, et al.: Endogenous airway acidi.cation: implications for asthma pathophysiology. Am J Respir Crit Care Med 2000, 161(3 Pt 1):694–699.

    PubMed  CAS  Google Scholar 

  17. Gaston B, Reilly J, Drazen JM, et al.: Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci U S A 1993, 90:10957–10961. A highly referenced seminal work introducing nitrosothiol biology to the respiratory community.

    Article  PubMed  CAS  Google Scholar 

  18. Herve P, Denjean A, Jian R, et al.: Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. Am Rev Respir Dis 1986, 134:986–989.

    PubMed  CAS  Google Scholar 

  19. Dykhuizen RS, Fraser A, McKenzie H, et al.: Helicobacter pylori is killed by nitrite under acidic conditions. Gut 1998, 42:334–337.

    Article  PubMed  CAS  Google Scholar 

  20. Doherty J, Carraro S, Hunt JF, Gaston B: Th1 cytokineinduced airway epithelial acidi.cation is nitric oxide synthase dependent. Am J Respir Crit Care Med 2005, A585.

  21. Burvall K, Palmberg L, Larsson K: Metabolic activation of A549 human airway epithelial cells by organic dust: a study based on microphysiometry. Life Sci 2002, 71:299–309.

    Article  PubMed  CAS  Google Scholar 

  22. Acevedo F: Exhaled breath condensate (EBC): changes in magnesium, pH and conductivity after exposure to swine house dust or inhaled LPS. Eur Respir J 2005, 26:P4669.

    Google Scholar 

  23. Undem BJ, Carr MJ: The role of nerves in asthma. Curr Allergy Asthma Rep 2002, 2:159–165.

    Article  PubMed  Google Scholar 

  24. Ricciardolo FLM, Rado V, Fabbri LM, et al.: Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide. Am J Respir Crit Care Med 1999, 159:557–562.

    PubMed  CAS  Google Scholar 

  25. Groneberg DA, Niimi A, Dinh QT, et al.: Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough. Am J Respir Crit Care Med 2004, 170:1276–1280.

    Article  PubMed  Google Scholar 

  26. Avidan B, Sonnenberg A, Schnell TG, Sontag SJ: Temporal associations between coughing or wheezing and acid re.ux in asthmatics. Gut 2001, 49:767–772.

    Article  PubMed  CAS  Google Scholar 

  27. Littner MR, Leung FW, Ballard ED, 2nd, et al.: Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid re.ux symptoms. Chest 2005, 128:1128–1135.

    Article  PubMed  CAS  Google Scholar 

  28. Harding SM: Gastroesophageal re.ux as an asthma trigger: acid stress. Chest 2004, 126:1398–1399.

    Article  PubMed  Google Scholar 

  29. Heading RC Review article: diagnosis and clinical investigation of gastro-oesophageal re.ux disease: a European view. Aliment Pharmacol Ther 2004, 20(Suppl 8):9–13.

    Article  PubMed  Google Scholar 

  30. Kiljander TO: The role of proton pump inhibitors in the management of gastroesophageal re.ux disease-related asthma and chronic cough. Am J Med 2003, 115(Suppl 3A):65S-71S.

    Article  PubMed  CAS  Google Scholar 

  31. Harding SM, Richter JE, Guzzo MR, et al.: Asthma and gastroesophageal re.ux: acid suppressive therapy improves asthma outcome. Am J Med 1996, 100:395–405.

    Article  PubMed  CAS  Google Scholar 

  32. Schnatz PF, Castell JA, Castell DO: Pulmonary symptoms associated with gastroesophageal re.ux: use of ambulatory pH monitoring to diagnose and to direct therapy. Am J Gastroenterol 1996, 91:1715–1718.

    PubMed  CAS  Google Scholar 

  33. Jack CI, Calverley PM, Donnelly RJ, et al.: Simultaneous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal re.ux. Thorax 1995, 50:201–204.

    PubMed  CAS  Google Scholar 

  34. Boyle JT, Tuchman DN, Altschuler SM, et al.: Mechanisms for the association of gastroesophageal re.ux and bronchospasm. Am Rev Respir Dis 1985, 131:S16-S20.

    PubMed  CAS  Google Scholar 

  35. Tuchman DN, Boyle JT, Pack AI, et al.: Comparison of airway responses following tracheal or esophageal acidi.cation in the cat. Gastroenterology 1984, 87:872–881.

    PubMed  CAS  Google Scholar 

  36. Ishikawa T, Sekizawa SI, Sant’Ambrogio FB, Sant’Ambrogio G: Larynx vs. esophagus as re.exogenic sites for acidinduced bronchoconstriction in dogs. J Appl Physiol 1999, 86:1226–1230.

    Article  PubMed  CAS  Google Scholar 

  37. Patterson RN, Johnston BT, MacMahon J, et al.: Oesophageal pH monitoring is of limited value in the diagnosis of "re.ux-cough". Eur Respir J 2004, 24:724–727.

    Article  PubMed  CAS  Google Scholar 

  38. Shaker R, Dodds WJ, Ren J, et al.: Esophagoglottal closure re.ex: a mechanism of airway protection. Gastroenterology 1992, 102:857–861.

    PubMed  CAS  Google Scholar 

  39. Halstead LA: Extraesophageal manifestations of GERD: diagnosis and therapy. Drugs Today (Barc) 2005, 41(Suppl B):19–26.

    Google Scholar 

  40. Laheij RJ, Sturkenboom MC, Hassing RJ, et al.: Risk of community-acquired pneumonia and use of gastric acidsuppressive drugs. JAMA 2004, 292:1955–1960.

    Article  PubMed  CAS  Google Scholar 

  41. Borrill Z, Starkey C, Vestbo J, Singh D: Reproducibility of exhaled breath condensate pH in chronic obstructive pulmonary disease. Eur Respir J 2005, 25:269–274.

    Article  PubMed  CAS  Google Scholar 

  42. Kostikas K, Papatheodorou G, Ganas K, et al.: pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med 2002, 165:1364–1370.

    Article  PubMed  Google Scholar 

  43. Paget-Brown A, Ngamtrakulpanit L, Smith A, et al.: Normative data for pH of exhaled breath condensate. Chest 2005, In press.

  44. Vaughan J, Ngamtrakulpanit L, Pajewski TN, et al.: Exhaled breath condensate pH is a robust and reproducible assay of airway acidity. Eur Respir J 2003, 22:889–894.

    Article  PubMed  CAS  Google Scholar 

  45. Wells K, Vaughan J, Pajewski TN, et al.: Exhaled breath condensate pH assays are not in.uenced by oral ammonia. Thorax 2005, 60:27–31.

    Article  PubMed  CAS  Google Scholar 

  46. Kostikas K, Papatheodorou G, Ganas K, et al.: pH in expired breath condensate of patients with inflammatory airway diseases. Eur Respir J 2001, 18(Suppl33):248S.

    Google Scholar 

  47. Hunt JF, Erwin E, Palmer L, et al.: Expression and activity of pH-regulatory glutaminase in the human airway epithelium. Am J Respir Crit Care Med 2002, 165:101–107.

    PubMed  Google Scholar 

  48. Horvath I, Hunt J, Barnes PJ: Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J 2005, 26:523–58. Recently published extensive report from the Joint American Thoracic Society/European Respiratory Society Task Force on Exhaled Breath Condensate

    Article  PubMed  CAS  Google Scholar 

  49. Crowle AJ, Dahl R, Ross E, May MH: Evidence that vesicles containing living, virulent Mycobacterium tuberculosis or Mycobacterium avium in cultured human macrophages are not acidic. Infect Immun 1991, 59:1823–1831.

    PubMed  CAS  Google Scholar 

  50. Papadopoulos NG, Stanciu LA, Papi A, et al.: A defective type 1 response to rhinovirus in atopic asthma. Thorax 2002, 57:328–332.

    Article  PubMed  CAS  Google Scholar 

  51. Klebanoff SJ: Reactive nitrogen intermediates and antimicrobial activity: role of nitrite. Free Radic Biol Med 1993, 14:351–360.

    Article  PubMed  CAS  Google Scholar 

  52. Heymann PW, Carper HT, Murphy DD, et al.: Viral infections in relation to age, atopy, and the season of admission among children hospitalized for wheezing. J Allergy Clin Immunol 2004, 114:239–247.

    Article  PubMed  Google Scholar 

  53. Ngamtrakulpanit L, Vaughan JW, Nguyen A, et al.: Exhaled breath condensate acidi.cation during rhinovirus cold. Am J Respir Crit Care Med 2003, 167:A446.

    Google Scholar 

  54. Ischiropoulos H, Zhu L, Chen J, et al.: Peroxynitritemediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 1992, 298:431–437.

    Article  PubMed  CAS  Google Scholar 

  55. Henderson EM, Gaston B: SNOR and wheeze: The asthma enzyme? Trends Mol Med 2005, Oct 6 [Epub ahead of print].

  56. Que LG, Liu L, Yan Y, et al.: Protection from experimental asthma by an endogenous bronchodilator. Science 2005, 308:1618–1621.

    Article  PubMed  CAS  Google Scholar 

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Hunt, J. Airway acidification: Interactions with nitrogen oxides and airway inflammation. Curr Allergy Asthma Rep 6, 47–52 (2006). https://doi.org/10.1007/s11882-006-0009-4

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